i3 Health is pleased to make this slide deck from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck, presented by Glenn J. Hanna, MD, Director, Center for Cancer Therapeutic Innovation (Early Drug Development Program)
Medical Oncologist, Center for Head & Neck Oncology
Dana-Farber Cancer Institute, and Deborah Wong, MD, PhD, Associate Clinical Professor of Medicine, Division of Hematology-Oncology, UCLA Medical Center, was presented at a live educational event at the 2024 Multidisciplinary Head and Neck Cancers Symposium. It will provide expert perspectives on harnessing immunotherapy in recurrent/metastatic HNSCC to provide comprehensive care.
1) Recent advances in head and neck cancers include the approval of immune checkpoint inhibitors like nivolumab and pembrolizumab for recurrent/metastatic disease based on results from clinical trials showing improved overall survival compared to standard chemotherapy.
2) The KEYNOTE-048 trial found that pembrolizumab in combination with chemotherapy led to significantly improved overall survival compared to EXTREME chemotherapy alone in patients with recurrent/metastatic head and neck squamous cell carcinoma.
3) Data from trials support pembrolizumab plus platinum-based chemotherapy as a new first-line standard of care for recurrent/metastatic head and neck cancer.
GU ASCO 2023 Targeted Therapy in mCRPC.pptxDoQuyenPhan1
Rana R. McKay is an associate professor of medicine and genitourinary oncology team lead who presented on emerging investigational targets and combinations for prostate cancer. The presentation discussed CDK4/6 inhibitors like abemaciclib, ribociclib, and palbociclib which drive cell cycle progression by phosphorylating Rb. Ongoing clinical trials were summarized that are exploring CDK4/6 inhibitors combined with standard therapies for metastatic castration-resistant prostate cancer or with novel agents like 177Lu-PSMA-617. Combining a PI3K/AKT/mTOR inhibitor, ipatasertib, with abiraterone was also discussed based on results from
Pembrolizumab - “Treatment of melanoma has never been this promising”Patwant Dhillon
Pembrolizumab is a monoclonal antibody that blocks the interaction between PD-1 receptors on T cells and PD-L1/PD-L2 ligands expressed by tumor cells. It was approved by the FDA based on results from the KEYNOTE-001 trial showing a 26% overall response rate in advanced melanoma patients who progressed on prior ipilimumab treatment. The trial found similar response rates of 26% for pembrolizumab doses of 2 mg/kg and 10 mg/kg every 3 weeks, with responses ongoing in 88% of patients after 8 months of follow up and a median progression free survival of 22 and 14 weeks respectively. Common adverse effects included fatigue, rash and pruritus.
Analyzing ASCO 2016: Developments, takeaways, and implications from the confe...Pharma Intelligence
In conjunction with a Key Opinion Leader, Dr. Peter Lee MD Chair, Department of Immuno-Oncology at City of Hope Comprehensive Cancer Center, CA, several Informa analysts discuss the major developments of the conference and key take-aways via a Webinar.
Watch our recording of Biomedtracker's Robert Jeng, Ph,D., Citeline's Allison Bruce, Scrip's Mary Jo Laffler, and Datamonitor Healthcare's Zachary McLellan as they download and debrief following the always-exciting ASCO weekend.
View and listen to the full webinar here https://www.youtube.com/watch?v=7yMsCb3R5X8
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...Fight Colorectal Cancer
This document summarizes key findings from the PRIME trial evaluating the addition of panitumumab to FOLFOX4 as first-line treatment for metastatic colorectal cancer. Biomarker analysis found that KRAS exon 2 wild-type tumors derived greater benefit from the addition of panitumumab, with a progression-free survival advantage compared to FOLFOX4 alone. Further biomarker testing found mutations in other RAS isoforms or BRAF reduced likelihood of benefit from panitumumab. The results support use of RAS/BRAF mutation testing to select patients for first-line anti-EGFR therapy in combination with chemotherapy.
1) The document summarizes a presentation on chemotherapy options and management issues in HER-2 negative metastatic breast cancer.
2) It discusses whether to use single-agent chemotherapy or combinations, and whether combinations should be given simultaneously or sequentially. The data shows combinations yield higher response rates but similar survival and more toxicity compared to sequential single agents.
3) New chemotherapy agents discussed include eribulin, ixabepilone, and nanoparticle albumin-bound paclitaxel (nab-paclitaxel). Biological agents discussed for HER-2 negative disease include PARP inhibitors and bevacizumab.
This document summarizes an academic presentation on recent therapeutic updates for metastatic urothelial cancer in 2018. It discusses standard of care for second-line treatment and recent results from Phase II and III trials of PD-1/PD-L1 inhibitors. Checkpoint inhibitors like atezolizumab, nivolumab, pembrolizumab, durvalumab and avelumab have received FDA approval for platinum-pretreated or cisplatin-ineligible metastatic urothelial cancer based on trials showing overall response rates of 15-29% and median overall survival of 7.7-15.9 months. Ongoing trials are exploring the potential for predictive biomarkers like PD-L1 expression and
1) Recent advances in head and neck cancers include the approval of immune checkpoint inhibitors like nivolumab and pembrolizumab for recurrent/metastatic disease based on results from clinical trials showing improved overall survival compared to standard chemotherapy.
2) The KEYNOTE-048 trial found that pembrolizumab in combination with chemotherapy led to significantly improved overall survival compared to EXTREME chemotherapy alone in patients with recurrent/metastatic head and neck squamous cell carcinoma.
3) Data from trials support pembrolizumab plus platinum-based chemotherapy as a new first-line standard of care for recurrent/metastatic head and neck cancer.
GU ASCO 2023 Targeted Therapy in mCRPC.pptxDoQuyenPhan1
Rana R. McKay is an associate professor of medicine and genitourinary oncology team lead who presented on emerging investigational targets and combinations for prostate cancer. The presentation discussed CDK4/6 inhibitors like abemaciclib, ribociclib, and palbociclib which drive cell cycle progression by phosphorylating Rb. Ongoing clinical trials were summarized that are exploring CDK4/6 inhibitors combined with standard therapies for metastatic castration-resistant prostate cancer or with novel agents like 177Lu-PSMA-617. Combining a PI3K/AKT/mTOR inhibitor, ipatasertib, with abiraterone was also discussed based on results from
Pembrolizumab - “Treatment of melanoma has never been this promising”Patwant Dhillon
Pembrolizumab is a monoclonal antibody that blocks the interaction between PD-1 receptors on T cells and PD-L1/PD-L2 ligands expressed by tumor cells. It was approved by the FDA based on results from the KEYNOTE-001 trial showing a 26% overall response rate in advanced melanoma patients who progressed on prior ipilimumab treatment. The trial found similar response rates of 26% for pembrolizumab doses of 2 mg/kg and 10 mg/kg every 3 weeks, with responses ongoing in 88% of patients after 8 months of follow up and a median progression free survival of 22 and 14 weeks respectively. Common adverse effects included fatigue, rash and pruritus.
Analyzing ASCO 2016: Developments, takeaways, and implications from the confe...Pharma Intelligence
In conjunction with a Key Opinion Leader, Dr. Peter Lee MD Chair, Department of Immuno-Oncology at City of Hope Comprehensive Cancer Center, CA, several Informa analysts discuss the major developments of the conference and key take-aways via a Webinar.
Watch our recording of Biomedtracker's Robert Jeng, Ph,D., Citeline's Allison Bruce, Scrip's Mary Jo Laffler, and Datamonitor Healthcare's Zachary McLellan as they download and debrief following the always-exciting ASCO weekend.
View and listen to the full webinar here https://www.youtube.com/watch?v=7yMsCb3R5X8
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...Fight Colorectal Cancer
This document summarizes key findings from the PRIME trial evaluating the addition of panitumumab to FOLFOX4 as first-line treatment for metastatic colorectal cancer. Biomarker analysis found that KRAS exon 2 wild-type tumors derived greater benefit from the addition of panitumumab, with a progression-free survival advantage compared to FOLFOX4 alone. Further biomarker testing found mutations in other RAS isoforms or BRAF reduced likelihood of benefit from panitumumab. The results support use of RAS/BRAF mutation testing to select patients for first-line anti-EGFR therapy in combination with chemotherapy.
1) The document summarizes a presentation on chemotherapy options and management issues in HER-2 negative metastatic breast cancer.
2) It discusses whether to use single-agent chemotherapy or combinations, and whether combinations should be given simultaneously or sequentially. The data shows combinations yield higher response rates but similar survival and more toxicity compared to sequential single agents.
3) New chemotherapy agents discussed include eribulin, ixabepilone, and nanoparticle albumin-bound paclitaxel (nab-paclitaxel). Biological agents discussed for HER-2 negative disease include PARP inhibitors and bevacizumab.
This document summarizes an academic presentation on recent therapeutic updates for metastatic urothelial cancer in 2018. It discusses standard of care for second-line treatment and recent results from Phase II and III trials of PD-1/PD-L1 inhibitors. Checkpoint inhibitors like atezolizumab, nivolumab, pembrolizumab, durvalumab and avelumab have received FDA approval for platinum-pretreated or cisplatin-ineligible metastatic urothelial cancer based on trials showing overall response rates of 15-29% and median overall survival of 7.7-15.9 months. Ongoing trials are exploring the potential for predictive biomarkers like PD-L1 expression and
Update on Systemic Therapy for Metastatic Pancreas AdenocarcinomaOSUCCC - James
The document discusses treatment options for metastatic pancreatic cancer. For first-line therapy, FOLFIRINOX is an option but is reserved for younger, healthier patients due to toxicity. Gemcitabine plus nab-paclitaxel is a preferred first-line option. For second-line therapy after progression on gemcitabine, nanoliposomal irinotecan plus 5-FU/LV has shown a survival benefit compared to 5-FU/LV alone. Molecular profiling of pancreatic tumors has identified subtypes that could help guide targeted therapies, and immune-based approaches also offer promise. The James Cancer Hospital is conducting clinical trials evaluating novel combinations for both first-line and second-line metastatic pancreatic cancer
Thanks to Prof. Chavdar Pavlov, MD, PhD, MScD - Department Head of Therapy, Head of the Centre for Evidence-Based Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia for helping organizing this event in Moscow.
Chair and Moderator, Petros Grivas, MD, PhD, Shilpa Gupta, MD, and Gary D. Steinberg, MD, prepared useful Practice Aids pertaining to bladder cancer for this CME/MOC activity titled “Breaking Down the Evidence in Bladder Cancer: Expert Perspectives and Practical Strategies on Immune, Targeted, and Antibody-Based Therapies.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/2WcJp3n. CME/MOC credit will be available until December 31, 2022.
Hitting the Target in HER2-Positive Metastatic Colorectal Canceri3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck will share the latest data and strategies for hitting the target in HER2-positive metastatic colorectal cancer. Dr. Christopher Lieu, Associate Professor at the University of Colorado Cancer Center, explores actionable targets to inform personalized care plans, guideline-recommended combination and sequencing strategies, adverse event monitoring and management, and more.
STATEMENT OF NEED
An estimated 153,020 new cases of colorectal cancer (CRC) are diagnosed annually, and 52,550 people die of the disease (Siegel et al, 2023). Approximately 22% of patients present with metastatic disease, which is associated with a dismal 5-year survival rate of 15% (SEER, 2022). Targeting biomarkers is a key strategy for expanding therapeutic options and improving outcomes in metastatic CRC. Human epidermal growth factor receptor 2 (HER2) amplification status and treatments targeting HER2 are some of the most recent additions to the arsenal of targeted therapy for this disease. This activity chaired by Christopher Lieu, MD, Associate Director of Clinical Research at the University of Colorado Cancer Center, will provide expert perspectives and practical guidance on treating HER2-positive metastatic CRC.
TARGET AUDIENCE
Oncologists, gastroenterologists, nurse practitioners, physician assistants, oncology nurses, and other health care professionals involved in the treatment of patients with colorectal cancer (CRC).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to
Distinguish actionable targets that can inform personalized care plans in metastatic CRC
Evaluate practice guidelines on treatment combinations and sequences for patients with metastatic CRC
Appraise emerging efficacy and safety data on novel targeted therapies for patients with HER2-positive metastatic CRC
Assess strategies for optimizing the safety and tolerability of novel targeted therapies for HER2-positive metastatic CRC
This document summarizes Dr. Frederick Hagemeister's presentation on anti-PD-1 and anti-CD30 antibodies for Hodgkin lymphoma from the 2014 American Society of Hematology annual meeting. It discusses preliminary results from phase 1 trials of nivolumab and pembrolizumab for relapsed/refractory HL, as well as trials combining brentuximab vedotin with chemotherapy for untreated advanced HL. Response rates to anti-PD-1 antibodies were high across studies. Combining brentuximab vedotin with ABVD/AVD showed promising efficacy in untreated patients with acceptable toxicity.
Ulcerative Colitis: Applying Guidelines in PracticeDevi Seal
This presentation developed was by David Rubin, MD, Millie Long, MD, MPH, and Anita Afzali, MD, MPH, for a CME activity titled, Ulcerative Colitis: Applying Guidelines in Practice
This document discusses advances in treatment for hepatitis C virus (HCV) infection. It provides information on:
- The primary goals of HCV treatment as viral eradication and prevention of liver disease progression.
- Definitions of sustained virological response (SVR) and response rates achieved with pegylated interferon and ribavirin treatment.
- New direct-acting antiviral drugs in development that target specific steps in the HCV lifecycle, including protease, polymerase, and NS5A inhibitors.
Chair and Presenter Neal D. Shore, MD, FACS, Sia Daneshmand, MD, and Guru P. Sonpavde, MD, prepared useful Practice Aids pertaining to bladder cancer for this CME/MOC/AAPA activity titled “Pioneering Precision Medicine in Bladder Cancer: Multidisciplinary Perspectives on Personalizing Patient Care.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at https://bit.ly/40qGkJH. CME/MOC/AAPA credit will be available until December 28, 2024.
El futuro del tratamiento del cáncer renal metastásico: inmunoterapia y terap...Mauricio Lema
Ponencia en el primer simposio de la Asociación Colombiana de Hematología y Oncología (ACHO) de cáncer genitourinario, Bogotá, septiembre 23 y 24 de 2016.
Palbociclib in Metastatic Breast CancerVibhay Pareek
1) The document discusses the role of palbociclib, a CDK4/6 inhibitor, in the treatment of metastatic breast cancer.
2) Key clinical trials showed that combining palbociclib with an aromatase inhibitor significantly improved progression-free survival compared to an aromatase inhibitor alone.
3) The BOLERO-2 trial found that adding everolimus, an mTOR inhibitor, to exemestane improved progression-free survival by 5 months and overall survival by 6 months compared to exemestane alone in metastatic breast cancer.
Adding carboplatin to paclitaxel chemotherapy for early triple-negative breast cancer (TNBC) improved pathological complete response rates and led to better long-term outcomes without increasing safety risks. Patients who achieved a complete pathological response had significantly improved event-free survival rates for at least 4.5 years after treatment, regardless of BRCA mutation status. These results support the inclusion of carboplatin in neoadjuvant chemotherapy for stages II-III TNBC.
Target Validation Academy Of Medical Sciences 1 Dec 2006Mike Romanos
An overview of the issues and approaches in selecting the best targets for drug discovery and validating them. Given at the Drug Discovery Forum held at the Royal Society, London and organised by the Academy of Medical Sciences
Panitumumab is a fully human monoclonal antibody that binds to the epidermal growth factor receptor (EGFR) with high affinity. It is approved as monotherapy or in combination with chemotherapy for wild-type KRAS metastatic colorectal cancer. Clinical trials have shown that panitumumab improves progression-free survival and overall survival when added to chemotherapy for first-line treatment of metastatic colorectal cancer patients with wild-type RAS tumors. Extended RAS testing beyond just KRAS exon 2 is important to identify patients most likely to benefit from panitumumab therapy. Common side effects include dermatological toxicities.
1) The PALOMA-3 trial evaluated the combination of palbociclib plus fulvestrant versus placebo plus fulvestrant for the treatment of hormone receptor-positive, HER2-negative advanced breast cancer that had progressed on previous endocrine therapy.
2) A total of 521 postmenopausal women were randomly assigned in a 2:1 ratio to receive either palbociclib plus fulvestrant or placebo plus fulvestrant.
3) An interim analysis found a statistically significant improvement in progression-free survival with the palbociclib combination, leading the data monitoring committee to recommend early termination of the trial in favor of the palbocic
This document summarizes results from the AURA-LV clinical trial studying the efficacy and safety of voclosporin in treating lupus nephritis. The trial found that patients receiving 23.7 mg of voclosporin twice daily were over twice as likely to achieve complete renal remission at 24 weeks compared to the placebo group. They were also more likely to achieve partial remission and saw faster time to response. At 48 weeks, the low-dose voclosporin group maintained higher remission rates and saw continued improvement in proteinuria levels over time, demonstrating voclosporin's potential as a new treatment for lupus nephritis.
1) Recent immunotherapy advances for advanced NSCLC include the approval of pembrolizumab as a first-line treatment for patients with PD-L1 expression ≥50% based on results from the KEYNOTE-024 trial showing improved progression-free and overall survival compared to chemotherapy.
2) The Phase III KEYNOTE-407 trial found that combining pembrolizumab with chemotherapy improved progression-free survival compared to chemotherapy alone in patients with untreated metastatic squamous NSCLC, regardless of PD-L1 expression level.
3) Combining chemotherapy with immunotherapy may enhance the immune response by increasing antigen presentation, disrupting immune evasion mechanisms, and improving outcomes compared to chemotherapy or immunotherapy alone.
Richard S. Finn, MD, Anthony El-Khoueiry, MD, and Josep M. Llovet, MD, PhD, prepared useful practice aids pertaining to hepatocellular carcinoma for this CME activity titled "Breaking the Paradox: Expanding Options and New Questions in HCC Management: Mapping the Pathways to Better Patient Outcomes." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2HU6L5K. CME credit will be available until February 14, 2020.
The document discusses new drug developments in subsets of breast cancer. It describes how breast cancer is being segmented into rare molecular subtypes defined by specific molecular alterations. This molecular segmentation is important for optimally developing targeted agents by enriching clinical trials for patients with the relevant molecular alteration. Several new drugs for treating specific breast cancer subtypes are mentioned, including drugs targeting HER2, angiogenesis, hormone receptors, and DNA repair pathways in triple negative breast cancer.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Exploring Novel Treatments for Rett Syndromei3 Health
This slide deck, led by Timothy John Feyma, MD, Pediatric Neurologist at Gilette Children’s Hospital, will explore novel treatments and quality-of-life improvement strategies for children and adults with Rett syndrome.
STATEMENT OF NEED
Rett syndrome is a rare, debilitating neurodevelopmental disorder almost always associated with a spontaneous mutation in the methyl-CpG-binding protein 2 (MECP2) gene on the X-chromosome. Affected individuals experience loss of purposeful hand skills, abnormalities in gait, loss of spoken language, and stereotypic hand movements, with more severe manifestations including seizures, autistic features, autonomic nervous system dysfunction, breathing abnormalities, sleep disturbances, and cardiac abnormalities. While therapies for Rett syndrome are being investigated in clinical trials and have demonstrated modest benefit, no curative or effective disease-modifying treatments currently exist (Petriti et al, 2023). Therefore, the multidisciplinary team is challenged with the optimal management of complex comorbidities that persist throughout patients’ lives. This activity chaired by Timothy John Feyma, MD, Pediatric Neurologist at Gilette Children’s Hospital, will explore novel treatments and quality-of-life improvement strategies for children and adults with Rett syndrome.
TARGET AUDIENCE
Pediatric and adult neurologists, pediatricians, internists, family physicians, child and adult psychiatrists, nurse practitioners, physician assistants, nurses, and other health care professionals involved in the treatment of children and adults with Rett syndrome.
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to
Identify distinguishing features of Rett syndrome that can inform early and accurate diagnosis
Evaluate the safety, efficacy, and clinical utility of novel and emerging treatments for Rett syndrome in children and adults
Devise strategies to monitor and manage Rett syndrome symptoms in children and adults
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Semelhante a Recurrent/Metastatic HNSCC: Harnessing Immunotherapy in Comprehensive Care
Update on Systemic Therapy for Metastatic Pancreas AdenocarcinomaOSUCCC - James
The document discusses treatment options for metastatic pancreatic cancer. For first-line therapy, FOLFIRINOX is an option but is reserved for younger, healthier patients due to toxicity. Gemcitabine plus nab-paclitaxel is a preferred first-line option. For second-line therapy after progression on gemcitabine, nanoliposomal irinotecan plus 5-FU/LV has shown a survival benefit compared to 5-FU/LV alone. Molecular profiling of pancreatic tumors has identified subtypes that could help guide targeted therapies, and immune-based approaches also offer promise. The James Cancer Hospital is conducting clinical trials evaluating novel combinations for both first-line and second-line metastatic pancreatic cancer
Thanks to Prof. Chavdar Pavlov, MD, PhD, MScD - Department Head of Therapy, Head of the Centre for Evidence-Based Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia for helping organizing this event in Moscow.
Chair and Moderator, Petros Grivas, MD, PhD, Shilpa Gupta, MD, and Gary D. Steinberg, MD, prepared useful Practice Aids pertaining to bladder cancer for this CME/MOC activity titled “Breaking Down the Evidence in Bladder Cancer: Expert Perspectives and Practical Strategies on Immune, Targeted, and Antibody-Based Therapies.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/2WcJp3n. CME/MOC credit will be available until December 31, 2022.
Hitting the Target in HER2-Positive Metastatic Colorectal Canceri3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck will share the latest data and strategies for hitting the target in HER2-positive metastatic colorectal cancer. Dr. Christopher Lieu, Associate Professor at the University of Colorado Cancer Center, explores actionable targets to inform personalized care plans, guideline-recommended combination and sequencing strategies, adverse event monitoring and management, and more.
STATEMENT OF NEED
An estimated 153,020 new cases of colorectal cancer (CRC) are diagnosed annually, and 52,550 people die of the disease (Siegel et al, 2023). Approximately 22% of patients present with metastatic disease, which is associated with a dismal 5-year survival rate of 15% (SEER, 2022). Targeting biomarkers is a key strategy for expanding therapeutic options and improving outcomes in metastatic CRC. Human epidermal growth factor receptor 2 (HER2) amplification status and treatments targeting HER2 are some of the most recent additions to the arsenal of targeted therapy for this disease. This activity chaired by Christopher Lieu, MD, Associate Director of Clinical Research at the University of Colorado Cancer Center, will provide expert perspectives and practical guidance on treating HER2-positive metastatic CRC.
TARGET AUDIENCE
Oncologists, gastroenterologists, nurse practitioners, physician assistants, oncology nurses, and other health care professionals involved in the treatment of patients with colorectal cancer (CRC).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to
Distinguish actionable targets that can inform personalized care plans in metastatic CRC
Evaluate practice guidelines on treatment combinations and sequences for patients with metastatic CRC
Appraise emerging efficacy and safety data on novel targeted therapies for patients with HER2-positive metastatic CRC
Assess strategies for optimizing the safety and tolerability of novel targeted therapies for HER2-positive metastatic CRC
This document summarizes Dr. Frederick Hagemeister's presentation on anti-PD-1 and anti-CD30 antibodies for Hodgkin lymphoma from the 2014 American Society of Hematology annual meeting. It discusses preliminary results from phase 1 trials of nivolumab and pembrolizumab for relapsed/refractory HL, as well as trials combining brentuximab vedotin with chemotherapy for untreated advanced HL. Response rates to anti-PD-1 antibodies were high across studies. Combining brentuximab vedotin with ABVD/AVD showed promising efficacy in untreated patients with acceptable toxicity.
Ulcerative Colitis: Applying Guidelines in PracticeDevi Seal
This presentation developed was by David Rubin, MD, Millie Long, MD, MPH, and Anita Afzali, MD, MPH, for a CME activity titled, Ulcerative Colitis: Applying Guidelines in Practice
This document discusses advances in treatment for hepatitis C virus (HCV) infection. It provides information on:
- The primary goals of HCV treatment as viral eradication and prevention of liver disease progression.
- Definitions of sustained virological response (SVR) and response rates achieved with pegylated interferon and ribavirin treatment.
- New direct-acting antiviral drugs in development that target specific steps in the HCV lifecycle, including protease, polymerase, and NS5A inhibitors.
Chair and Presenter Neal D. Shore, MD, FACS, Sia Daneshmand, MD, and Guru P. Sonpavde, MD, prepared useful Practice Aids pertaining to bladder cancer for this CME/MOC/AAPA activity titled “Pioneering Precision Medicine in Bladder Cancer: Multidisciplinary Perspectives on Personalizing Patient Care.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at https://bit.ly/40qGkJH. CME/MOC/AAPA credit will be available until December 28, 2024.
El futuro del tratamiento del cáncer renal metastásico: inmunoterapia y terap...Mauricio Lema
Ponencia en el primer simposio de la Asociación Colombiana de Hematología y Oncología (ACHO) de cáncer genitourinario, Bogotá, septiembre 23 y 24 de 2016.
Palbociclib in Metastatic Breast CancerVibhay Pareek
1) The document discusses the role of palbociclib, a CDK4/6 inhibitor, in the treatment of metastatic breast cancer.
2) Key clinical trials showed that combining palbociclib with an aromatase inhibitor significantly improved progression-free survival compared to an aromatase inhibitor alone.
3) The BOLERO-2 trial found that adding everolimus, an mTOR inhibitor, to exemestane improved progression-free survival by 5 months and overall survival by 6 months compared to exemestane alone in metastatic breast cancer.
Adding carboplatin to paclitaxel chemotherapy for early triple-negative breast cancer (TNBC) improved pathological complete response rates and led to better long-term outcomes without increasing safety risks. Patients who achieved a complete pathological response had significantly improved event-free survival rates for at least 4.5 years after treatment, regardless of BRCA mutation status. These results support the inclusion of carboplatin in neoadjuvant chemotherapy for stages II-III TNBC.
Target Validation Academy Of Medical Sciences 1 Dec 2006Mike Romanos
An overview of the issues and approaches in selecting the best targets for drug discovery and validating them. Given at the Drug Discovery Forum held at the Royal Society, London and organised by the Academy of Medical Sciences
Panitumumab is a fully human monoclonal antibody that binds to the epidermal growth factor receptor (EGFR) with high affinity. It is approved as monotherapy or in combination with chemotherapy for wild-type KRAS metastatic colorectal cancer. Clinical trials have shown that panitumumab improves progression-free survival and overall survival when added to chemotherapy for first-line treatment of metastatic colorectal cancer patients with wild-type RAS tumors. Extended RAS testing beyond just KRAS exon 2 is important to identify patients most likely to benefit from panitumumab therapy. Common side effects include dermatological toxicities.
1) The PALOMA-3 trial evaluated the combination of palbociclib plus fulvestrant versus placebo plus fulvestrant for the treatment of hormone receptor-positive, HER2-negative advanced breast cancer that had progressed on previous endocrine therapy.
2) A total of 521 postmenopausal women were randomly assigned in a 2:1 ratio to receive either palbociclib plus fulvestrant or placebo plus fulvestrant.
3) An interim analysis found a statistically significant improvement in progression-free survival with the palbociclib combination, leading the data monitoring committee to recommend early termination of the trial in favor of the palbocic
This document summarizes results from the AURA-LV clinical trial studying the efficacy and safety of voclosporin in treating lupus nephritis. The trial found that patients receiving 23.7 mg of voclosporin twice daily were over twice as likely to achieve complete renal remission at 24 weeks compared to the placebo group. They were also more likely to achieve partial remission and saw faster time to response. At 48 weeks, the low-dose voclosporin group maintained higher remission rates and saw continued improvement in proteinuria levels over time, demonstrating voclosporin's potential as a new treatment for lupus nephritis.
1) Recent immunotherapy advances for advanced NSCLC include the approval of pembrolizumab as a first-line treatment for patients with PD-L1 expression ≥50% based on results from the KEYNOTE-024 trial showing improved progression-free and overall survival compared to chemotherapy.
2) The Phase III KEYNOTE-407 trial found that combining pembrolizumab with chemotherapy improved progression-free survival compared to chemotherapy alone in patients with untreated metastatic squamous NSCLC, regardless of PD-L1 expression level.
3) Combining chemotherapy with immunotherapy may enhance the immune response by increasing antigen presentation, disrupting immune evasion mechanisms, and improving outcomes compared to chemotherapy or immunotherapy alone.
Richard S. Finn, MD, Anthony El-Khoueiry, MD, and Josep M. Llovet, MD, PhD, prepared useful practice aids pertaining to hepatocellular carcinoma for this CME activity titled "Breaking the Paradox: Expanding Options and New Questions in HCC Management: Mapping the Pathways to Better Patient Outcomes." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2HU6L5K. CME credit will be available until February 14, 2020.
The document discusses new drug developments in subsets of breast cancer. It describes how breast cancer is being segmented into rare molecular subtypes defined by specific molecular alterations. This molecular segmentation is important for optimally developing targeted agents by enriching clinical trials for patients with the relevant molecular alteration. Several new drugs for treating specific breast cancer subtypes are mentioned, including drugs targeting HER2, angiogenesis, hormone receptors, and DNA repair pathways in triple negative breast cancer.
Semelhante a Recurrent/Metastatic HNSCC: Harnessing Immunotherapy in Comprehensive Care (20)
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Exploring Novel Treatments for Rett Syndromei3 Health
This slide deck, led by Timothy John Feyma, MD, Pediatric Neurologist at Gilette Children’s Hospital, will explore novel treatments and quality-of-life improvement strategies for children and adults with Rett syndrome.
STATEMENT OF NEED
Rett syndrome is a rare, debilitating neurodevelopmental disorder almost always associated with a spontaneous mutation in the methyl-CpG-binding protein 2 (MECP2) gene on the X-chromosome. Affected individuals experience loss of purposeful hand skills, abnormalities in gait, loss of spoken language, and stereotypic hand movements, with more severe manifestations including seizures, autistic features, autonomic nervous system dysfunction, breathing abnormalities, sleep disturbances, and cardiac abnormalities. While therapies for Rett syndrome are being investigated in clinical trials and have demonstrated modest benefit, no curative or effective disease-modifying treatments currently exist (Petriti et al, 2023). Therefore, the multidisciplinary team is challenged with the optimal management of complex comorbidities that persist throughout patients’ lives. This activity chaired by Timothy John Feyma, MD, Pediatric Neurologist at Gilette Children’s Hospital, will explore novel treatments and quality-of-life improvement strategies for children and adults with Rett syndrome.
TARGET AUDIENCE
Pediatric and adult neurologists, pediatricians, internists, family physicians, child and adult psychiatrists, nurse practitioners, physician assistants, nurses, and other health care professionals involved in the treatment of children and adults with Rett syndrome.
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to
Identify distinguishing features of Rett syndrome that can inform early and accurate diagnosis
Evaluate the safety, efficacy, and clinical utility of novel and emerging treatments for Rett syndrome in children and adults
Devise strategies to monitor and manage Rett syndrome symptoms in children and adults
Leveraging the Growing Arsenal of Adjuvant Therapies for Early-Stage NSCLCi3 Health
3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by, Dr. Helena A. Yu, Associate Attending Physician at Memorial Sloan Kettering Cancer Center, will provide insights into strategies for leveraging the growing arsenal of adjuvant therapies for early-stage non–small cell lung cancer (NSCLC), including treatment selection and adverse event management.
STATEMENT OF NEED
Lung cancer is the second most commonly diagnosed cancer and the leading cause of death for men and women worldwide. In the United States, non–small cell lung cancer (NSCLC) accounts for 81% of all lung cancer diagnoses (Cancer.net, 2023). Therapeutic options, survival rates, and outcomes for NSCLC are dramatically impacted by disease stage. For patients with early-stage disease, radical surgery is the mainstay of treatment; however, patients have a significant risk of relapse following surgery and local treatment. Numerous novel therapeutic approaches, including the use of molecular biomarkers and the development of targeted agents and immune checkpoint inhibitors, are under investigation for early-stage NSCLC, contributing to a growing arsenal of treatment options for this disease (Indini et al, 2020). In this visiting faculty meeting series chaired by Helena A. Yu, MD, Associate Attending Physician at Memorial Sloan Kettering Cancer Center, speakers will provide expert perspectives on diagnosis, identification of biomarkers, and efficacy and safety data of novel adjuvant therapies to improve survival outcomes for patients with early-stage NSCLC.
TARGET AUDIENCE
Medical oncologists, radiation oncologists, surgical oncologists, pulmonologists, nurse practitioners, physician assistants, oncology nurses, and other health care professionals involved in the treatment of patients with non–small cell lung cancer (NSCLC).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to
Identify the correct tumor stage and appropriate management approach for NSCLC based on the latest evidence
Distinguish biomarkers for early-stage NSCLC that can inform individualized treatment strategies
Appraise efficacy and safety data of novel adjuvant therapies for patients with NSCLC as elucidated by recent clinical trials
Apply strategies to prevent and mitigate adverse events associated with novel adjuvant therapies for early-stage NSCLC
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Leveraging the Growing Arsenal of Adjuvant
Therapies for Early-Stage NSCLC
Helena A. Yu, MD
Associate Attending Physician
Memorial Sloan Kettering Cancer Center
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Disclosures
Advisory board/panel: AbbVie, AstraZeneca, Black Diamond,
Blueprint, C4 Therapeutics, Cullinan, Daiichi Sankyo, Janssen, Taiho,
Takeda
Grants/research support: AstraZeneca, Black Diamond, Blueprint,
Cullinan, Daiichi Sankyo, Erasca, Janssen, Novartis, Pfize
Exploring Advances in the Early Diagnosis and Treatment of Alzheimer Disease ...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
In this slide deck, discover new insights into early diagnosis, emerging treatment modalities, and supportive care services for Alzheimer disease. An expert faculty member will discuss biological and clinical distinctions between mild cognitive impairment, dementia, and Alzheimer disease; methods for timely diagnosis; clinical trial data on novel monoclonal antibody therapies; prevention and management of side effects associated with monoclonal antibody therapies, including ARIA, and interdisciplinary support services for improving quality of life.
STATEMENT OF NEED
Alzheimer disease, the most common form of dementia among older adults, is a slowly progressive neurogenerative disease that affects approximately 6 million Americans aged 65 and older (Rajan et al, 2021). Symptoms of Alzheimer disease include memory loss, confusion, impulsive behavior, difficulty with language, mood and personality changes, hallucinations, and increased anxiety or aggression, with severe symptoms such as physical decline, difficulty swallowing, and inability to communicate developing as the disease progresses into its final stages (NIA, 2023). While new therapeutic agents have recently emerged to slow the progression of Alzheimer disease by targeting its underlying causes, the disease remains incurable, and the demands of day-to-day care place significant strain on both patients and their families and caregivers. Therefore, it is critical that clinicians remain up to date on early diagnosis, emerging treatment modalities, and supportive care services in order to provide optimal care for their patients. In this live webinar chaired by Nathaniel Chin, MD, Associate Professor of Medicine in the Division of Geriatrics and Gerontology at the University of Wisconsin-Madison, speakers will explore advances in the diagnosis and treatment of Alzheimer disease.
TARGET AUDIENCE
Geriatricians, neurologists, primary care physicians, psychiatrists, psychogeriatricians, nurse practitioners, physician assistants, nurses, and other health care professionals (HCPs) involved in the treatment of patients with Alzheimer disease (AD).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Utilize diagnostic methods that enable the timely identification of early Alzheimer disease (AD)
Evaluate the clinical utility of novel and emerging DMTs for the treatment of individual patients with early AD
Apply strategies to enhance interdisciplinary care for patients with early AD
Enhancing MRD Testing in Hematologic Malignancies: When Negativity is a Posit...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This expert CME-approved slide deck, presented by Noopur Raje, MD, Director of the Center for Multiple Myeloma at Massachusetts General Cancer Center, will explore the current and emerging roles of MRD testing in hematologic malignancies. She presents the ongoing questions and latest data regarding the clinical utility of MRD testing in prognosis and treatment.
STATEMENT OF NEED
Measurable residual disease (MRD) is defined as the persistence of cancer cells at levels below morphologic detection after treatment. For patients with hematologic malignancies, MRD testing is increasingly being used to predict disease progression, monitor disease status, and evaluate treatment options (Dekker et al, 2023). Questions about current and future roles of MRD testing abound, including validation of assays, such as next-generation sequencing, machine learning, and flow cytometry; standardization of collection methods and modalities; considerations for clinical trial design and statistical analyses; and improved understanding of the roles of MRD status and depth of response across hematologic malignancies (Dekker et al, 2023; Baines et al, 2023). It is critical for members of the multidisciplinary cancer care team to stay up-to-date on the latest data regarding the clinical utility of MRD testing in prognosis and treatment. In this CME-approved activity, Noopur Raje, MD, Director of the Center for Multiple Myeloma at Massachusetts General Cancer Center, will explore the current and emerging roles of MRD testing in hematologic malignancies.
TARGET AUDIENCE
Medical oncologists, hematologists, pathologists, and other health care professionals involved in the treatment of patients with hematologic malignancies.
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Distinguish the advantages and limitations of current MRD detection methods
Evaluate consensus recommendations on indications for MRD testing in hematologic malignancies
Explain the current and potential roles of MRD status and depth of response as a biomarker in clinical trials
Describe mechanisms of drug resistance/loss of response to BCMA-directed therapies
Assess the clinical utility of MRD in prognosis and treatment of selected hematologic malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma
Slowing Progression of Chronic Kidney Disease Through Value-Based Carei3 Health
i3 Health is pleased to make this infographic from this activity available for use as a non-accredited self-study or teaching resource.
This two module CPE activity brings two leading pharmacists together to discuss the slowing progression of Chronic Kidney disease through value-based care.
In Module 1 of this activity, Jeff Sperry, PharmD, BCPS, Clinical Pharmacist at UCHealth Memorial Hospital, will explore risk factors contributing to CKD, efficacy and safety of novel therapies for slowing kidney function decline, and evidence-based strategies for management of CKD complications.
In Module 2 Justin J. Bioc, PharmD, BCPS, BCGP, RPh, Head of Clinical Pharmacy at Devoted Health, will explore the cost-effectiveness of novel therapies indicated to slow kidney function decline and strategies that maximize collaboration between payers and providers to optimize the care of patients with CKD.
Managing Immune-Related Adverse Events to Ensure Optimal Cancer Immunotherapy...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck, presented by Blanca Ledezma, MSN, NP, AOCNP® Nurse Practitioner
Hematology/Oncology
University of California, Los Angeles (UCLA) Health, will provide insight into the nurse’s view on managing immune-related adverse events to ensure optimal cancer immunotherapy outcomes.
Immune checkpoint inhibitors, which alter immune regulatory pathways and promote cell-mediated destruction of tumor cells, have revolutionized the treatment of cancer in recent years, with numerous therapeutic agents approved and several targets under investigation (Chennamadhavuni et al, 2022). However, up to 90% of patients receiving immune checkpoint inhibitors experience immune-related adverse events, which can affect a wide variety of organ systems and can occur at any time during treatment or even after treatment completion (NCCN, 2023). Immune-related adverse events are associated with significant morbidity as well as the risk of therapy discontinuation, which can have an unpredictable impact on patients’ disease course. Therefore, it is critical for nurses to understand the mechanism, identification, and timely management of immune-related adverse events (Shankar et al, 2022). In this activity presented by Blanca Ledezma, MSN, NP, AOCNP®, Nurse Practitioner at the University of California, Los Angeles (UCLA) Health, will provide insight into the nurse’s view on managing immune-related adverse events to ensure optimal cancer immunotherapy outcomes.
TARGET AUDIENCE
Oncology nurses, nurse practitioners, clinical nurse specialists, and other health care professionals involved in the management of patients with immune-related adverse events (IRAEs).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Discuss how the mechanisms of action of immunotherapies influence their safety profile
Identify risk factors predisposing patients to IRAEs
Distinguish IRAEs from chemotherapy- and targeted therapy-related adverse events
Coordinate with the interdisciplinary health care team to apply evidence-based guidelines and best practices in personalized nursing management plans for patients with IRAEs
Develop patient counseling strategies promoting awareness, self-monitoring, and escalated reporting of IRAEs
Putting the Freeze on Cold Agglutinin Diseasei3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by, Catherine M. Broome, MD, Associate Professor of Medicine at Georgetown University School of Medicine, will provide expert guidance on diagnostic features, current treatment standards, emerging therapies, and supportive care strategies for patients with cold agglutinin disease (CAD). Start the activity now!
STATEMENT OF NEED
Cold agglutinin disease (CAD) is a rare subtype of autoimmune hemolytic anemia (AIHA) in which antibodies cause hemolysis at cold temperatures, generally between 37º to 39º Fahrenheit. Approximately 1 in a million people are affected by CAD annually, with onset usually occurring between the ages of 40 and 80 years. Individuals commonly experience fatigue, dizziness, palpitations, and shortness of breath caused by the anemia; jaundice caused by degradation of hemoglobin into bilirubin; and sweating, coldness, or painful discoloration of their fingers, toes, ankles, and wrists triggered by exposure to cold (NORD, 2020). While progress has been made in recent years in understanding the pathogenesis of CAD, consensus recommendations based on randomized trials are needed for improving treatment outcomes and reducing symptom burden (Berentsen, 2021). In this Hematology/Oncology Fellows Lecture Series chaired by Catherine Broome, MD, Associate Professor of Medicine at Georgetown University School of Medicine, faculty will provide expert perspectives on optimizing the diagnosis, treatment, and supportive care of CAD.
TARGET AUDIENCE
Hematology fellows, attending faculty, and other health care professionals involved in the treatment of patients with cold agglutinin disease (CAD).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Evaluate the clinical and laboratory features of CAD that can inform timely and accurate diagnosis
Discuss the pathophysiology of CAD and the scientific rationale for targeting the classical complement pathway
Appraise the efficacy and safety of novel complement inhibitors for CAD as elucidated by recent studies
Assess strategies for managing anemia, cold-induced circulatory symptoms, and treatment-related adverse events to optimize the clinical outcomes of patients with CAD
Faculty
Catherine M. Broome, MD
Professor of Medicine
Georgetown University School of Medicine
Virtual Tumor Board: Multidisciplinary Management of Advanced Soft Tissue Sar...i3 Health
i3 Health is pleased to make the Clinical Decision Aid from this activity available for use as a non-accredited self-study or teaching resource.
Gain insights and perspectives from this multidisciplinary panel of experts as they discuss cases and explore strategies to optimize treatment outcomes for patients with advanced soft tissue sarcoma. This distinguished Virtual Tumor Board features Shreyaskumar R. Patel, MD, Medical Director of the Sarcoma Center at the University of Texas MD Anderson Cancer Center; Kathleen Polson, NP, Nurse Practitioner at Dana-Farber Cancer Institute; and Brian Rubin, MD, PhD, Professor of Pathology at Cleveland Clinic Cancer Center
STATEMENT OF NEED
Sarcomas, which represent 1% to 2% of adult cancers, are a rare, heterogeneous group of neoplasms originating in the connective tissue. Soft tissue sarcomas, which begin in the muscle, tendons, fat, lymph, blood vessels, and nerves, encompass more than 80 histological subtypes. Approximately 25% of patients develop metastatic disease after curative-intent surgery, and for these patients, treatment options are limited and prognosis is very poor. In recent decades, the identification of genetic alterations in soft tissue sarcoma has led to the rise of targeted therapy, significantly expanding the therapeutic landscape. Remaining up to date on pathological characteristics and emerging data on novel therapies is crucial (Riskjell et al, 2023; NCI, 2023). In this Virtual Tumor Board, Shreyaskumar R. Patel, MD, Medical Director of the Sarcoma Center at the University of Texas MD Anderson Cancer Center; Kathleen Polson, NP, Nurse Practitioner at Dana-Farber Cancer Institute; and Brian Rubin, MD, PhD, Professor of Pathology at Cleveland Clinic Cancer Center, will present cases and explore multidisciplinary strategies to optimize treatment outcomes for patients with advanced soft tissue sarcoma.
TARGET AUDIENCE
Medical/surgical/radiation oncologists, pathologists, nurse practitioners, physician assistants, oncology nurses, and other health care professionals involved in the treatment of patients with soft tissue sarcoma.
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to
Distinguish patient and tumor characteristics that can inform personalized therapeutic approaches in soft tissue sarcoma
Evaluate emerging data on novel therapies for soft tissue sarcoma
Appraise multidisciplinary strategies to optimize treatment outcomes of patients with advanced soft tissue sarcoma
FACULTY
Shreyaskumar R. Patel, MD
Robert R. Herring Distinguished Professor of Medicine
Center Medical Director, Sarcoma Center
The University of Texas
MD Anderson Cancer Center
Kathleen Polson, NP
Nurse Practitioner
Dana-Farber Cancer Institute
Brian Rubin, MD, PhD
Professor of Pathology
Chairman, Robert J. Tomsich Pathology and Laboratory Medicine Institute
Cleveland Clinic Cancer Center
Pathology and Oncology Expert Perspectives in the Management of Triple-Negati...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck, presented by Dr. Ira Bleiweiss, Chief of Breast Pathology at the University of Pennsylvania, and Dr. Sara Tolaney, Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, will feature expert pathology and oncology perspectives on the management of triple-negative breast cancer (TNBC), including case explorations and insights into frequently asked questions. Register today to hear these expert perspectives!
Statement of Need
Triple-negative breast cancer (TNBC) is an aggressive disease that accounts for approximately 10% to 15% of breast cancer diagnoses and is characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). TNBC is more common in Black women and in women under the age of 40 (ACS, 2023). Compared with other subtypes of invasive breast cancer, TNBC has high rates of metastasis and a poor prognosis. Due to the lack of hormone and receptor targets, therapeutic options are limited, and prognostication and treatment selection are complicated by the heterogeneity of the disease (Yang et al, 2022). In this live webinar, Dr. Sara Tolaney, Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, and Dr. Ira Bleiweiss, Chief of Breast Pathology at the Hospital of the University of Pennsylvania, will provide expert oncology and pathology perspectives on evidence-based strategies for diagnosis, treatment, and adverse event management for patients with TNBC.
TARGET AUDIENCE
Medical oncologists, surgical oncologists, radiation oncologists, pathologists, nurse practitioners, physician assistants, oncology nurses, and other health care professionals involved in the treatment of patients with triple-negative breast cancer (TNBC).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Evaluate receptor and expression status for prognostication and treatment selection in TNBC
Differentiate the pathological characteristics of the various types of TNBC
Select optimal therapy for TNBC based on shared goals, biomarker testing, and clinical data on novel therapies
Discuss strategies for timely recognition and mitigation of adverse events associated with novel TNBC therapies
Current Standards and New Directions in the Treatment of Acquired Thrombotic ...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
Gain insight and expertise in this presentation on acquired thrombotic thrombocytopenic purpura. Spero Cataland, MD, Professor of Clinical Internal Medicine and Director of Benign Hematology at The Ohio State University, will provide guidance on current treatment standards and will discuss emerging therapies with the potential to improve patient outcomes in aTTP.
STATEMENT OF NEED
Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening thrombotic microangiopathy with a rapid onset and progression and a mortality rate of 10% to 20% with prompt treatment. Onset of aTTP is characterized by severe thrombocytopenia, microangiopathic hemolytic anemia, and a constellation of associated symptoms including hemorrhage, neurologic and renal manifestations, cardiac abnormalities, and mesenteric ischemia (Joly et al, 2017). Survivors of first aTTP events tend to have relapse events which need to be controlled. Rapid recognition and immediate appropriate treatment are critical for achieving optimized outcomes in aTTP. In this activity chaired by Spero Cataland, MD, Professor of Clinical Internal Medicine and Director of Benign Hematology at The Ohio State University, expert faculty will provide insightful guidance on current treatment standards and will discuss emerging therapies with the potential to improve patient outcomes in aTTP.
TARGET AUDIENCE
Hematology fellows, attending faculty, and other health care professionals involved in the treatment of patients with acquired thrombotic thrombocytopenic purpura (aTTP).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to
Evaluate the clinical and laboratory features of aTTP that can inform timely and accurate diagnosis
Discuss how ADAMTS13 activity can be used to guide the management of aTTP
Assess the mechanism of action, efficacy, and safety of novel anti-von Willebrand factor nanobodies in aTTP as elucidated by recent clinical trials
Evaluate novel treatment combinations and sequences with the potential to improve the outcomes of patients with aTTP
Expert Guidance on Current Standards and New Directions in Newly Diagnosed Mu...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
Presented by leading expert Urvi Shah, MD, Assistant Attending in the Myeloma Service at Memorial Sloan Kettering Cancer Center, this slide deck will explore guidance on current standards and new directions in newly diagnosed multiple myeloma.
STATEMENT OF NEED
An estimated 35,730 new cases of multiple myeloma are diagnosed in the United States annually, and 12,590 people die of the disease (Siegel et al, 2023). Characterized by clonal proliferation of malignant plasma cells in the bone marrow, multiple myeloma is associated with anemia, renal insufficiency, bone destruction, and hypercalcemia, all of which significantly impact patients’ quality of life. The development of novel therapies and combinations in recent years, including anti-CD38 antibodies, has provided numerous therapeutic options for newly diagnosed multiple myeloma. However, the optimal selection of induction therapy and subsequent treatment sequencing for individual patients remains a challenge. Additionally, factors including age, frailty, comorbidities, transplant eligibility, treatment-related toxicities, and supportive care needs complicate treatment decisions (Costello et al, 2022). This hematology/oncology fellows lecture series will explore expert guidance on current standards and new directions in newly diagnosed multiple myeloma.
TARGET AUDIENCE
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with multiple myeloma.
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Assess guideline-recommended treatment combination and sequencing strategies in NDMM
Evaluate the role of minimal residual disease (MRD) assessment in NDMM treatment
Review the mechanism of action, efficacy, and safety of anti-CD38 monoclonal antibodies in the treatment of NDMM
Discuss strategies to monitor and manage treatment-related toxicities and optimize survivorship care
Leveraging BCMA-Directed Therapies for Improved Patient Outcomes in Relapsed/...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Rahul Banerjee, Assistant Professor at the University of Washington and Fred Hutchinson Cancer Center, will provide a case-based discussion on leveraging BCMA-directed antibody-drug conjugates, CAR T-cell therapies, and bispecific T-cell engagers to improve outcomes for patients with multiple myeloma in need of additional treatment options.
STATEMENT OF NEED
Multiple myeloma is a disease that remains incurable for most patients, many of whom become refractory to the majority of available treatments (Kumar et al, 2022). It is estimated that 35,730 new cases of multiple myeloma are diagnosed in the United States annually, and 12,590 people die of the disease (Siegel et al, 2023). Agents targeting B-cell maturation antigen (BCMA), including antibody-drug conjugates (ADCs), chimeric antigen receptor (CAR) T-cell therapies, and bispecific T-cell engagers, represent a promising therapy class for patients in need of additional treatment options, including those with higher genetic risk and heterogeneity (Kumar et al, 2022). This activity led by Rahul Banerjee, MD, FACP, Assistant Professor in the Division of Medical Oncology at the University of Washington and Fred Hutchinson Cancer Center, will provide strategies for leveraging BCMA-directed therapies for improved patient outcomes in relapsed/refractory multiple myeloma.
TARGET AUDIENCE
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with multiple myeloma (MM).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Evaluate the mechanisms of action, efficacy, and safety of BCMA-directed therapies in relapsed/refractory MM
Assess guideline-recommended combination and sequential treatment strategies for relapsed/refractory MM
Identify risk factors for the development of treatment-specific adverse events with different classes of BCMA-directed therapies
Describe mechanisms of drug resistance/loss of response to BCMA-directed therapies
Examine the roles of gene expression profiling, soluble BCMA, and measurable residual disease (MRD) in clinical practice.
Optimizing Therapeutic Strategies in Castration-Resistant Prostate Canceri3 Health
This activity will discuss emerging efficacy and safety data on novel therapies for nmCRPC and mCRPC, strategies to manage adverse events, and the role of imaging studies and PSA testing in evaluating treatment response.
Optimizing Treatment Sequencing for Patients With Relapsed/ Refractory Multi...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Shaji Kumar, MD, Professor of Hematological Malignancies
Mayo Clinic Cancer Center, offers expert insight on the assessment of MM, emerging and current therapies, cutting edge approaches to personalized treatments plans, and much more.
Tailoring Therapy for Follicular Lymphoma Based on the Latest Evidencei3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This live or zoom broadcasted hematology/oncology fellowship program will bring an expert faculty member to your institution to discuss the latest developments and expert perspectives in the treatment of follicular lymphoma.
Reimagining Your Library Space: How to Increase the Vibes in Your Library No ...Diana Rendina
Librarians are leading the way in creating future-ready citizens – now we need to update our spaces to match. In this session, attendees will get inspiration for transforming their library spaces. You’ll learn how to survey students and patrons, create a focus group, and use design thinking to brainstorm ideas for your space. We’ll discuss budget friendly ways to change your space as well as how to find funding. No matter where you’re at, you’ll find ideas for reimagining your space in this session.
Walmart Business+ and Spark Good for Nonprofits.pdfTechSoup
"Learn about all the ways Walmart supports nonprofit organizations.
You will hear from Liz Willett, the Head of Nonprofits, and hear about what Walmart is doing to help nonprofits, including Walmart Business and Spark Good. Walmart Business+ is a new offer for nonprofits that offers discounts and also streamlines nonprofits order and expense tracking, saving time and money.
The webinar may also give some examples on how nonprofits can best leverage Walmart Business+.
The event will cover the following::
Walmart Business + (https://business.walmart.com/plus) is a new shopping experience for nonprofits, schools, and local business customers that connects an exclusive online shopping experience to stores. Benefits include free delivery and shipping, a 'Spend Analytics” feature, special discounts, deals and tax-exempt shopping.
Special TechSoup offer for a free 180 days membership, and up to $150 in discounts on eligible orders.
Spark Good (walmart.com/sparkgood) is a charitable platform that enables nonprofits to receive donations directly from customers and associates.
Answers about how you can do more with Walmart!"
A review of the growth of the Israel Genealogy Research Association Database Collection for the last 12 months. Our collection is now passed the 3 million mark and still growing. See which archives have contributed the most. See the different types of records we have, and which years have had records added. You can also see what we have for the future.
Main Java[All of the Base Concepts}.docxadhitya5119
This is part 1 of my Java Learning Journey. This Contains Custom methods, classes, constructors, packages, multithreading , try- catch block, finally block and more.
This presentation includes basic of PCOS their pathology and treatment and also Ayurveda correlation of PCOS and Ayurvedic line of treatment mentioned in classics.
ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...PECB
Denis is a dynamic and results-driven Chief Information Officer (CIO) with a distinguished career spanning information systems analysis and technical project management. With a proven track record of spearheading the design and delivery of cutting-edge Information Management solutions, he has consistently elevated business operations, streamlined reporting functions, and maximized process efficiency.
Certified as an ISO/IEC 27001: Information Security Management Systems (ISMS) Lead Implementer, Data Protection Officer, and Cyber Risks Analyst, Denis brings a heightened focus on data security, privacy, and cyber resilience to every endeavor.
His expertise extends across a diverse spectrum of reporting, database, and web development applications, underpinned by an exceptional grasp of data storage and virtualization technologies. His proficiency in application testing, database administration, and data cleansing ensures seamless execution of complex projects.
What sets Denis apart is his comprehensive understanding of Business and Systems Analysis technologies, honed through involvement in all phases of the Software Development Lifecycle (SDLC). From meticulous requirements gathering to precise analysis, innovative design, rigorous development, thorough testing, and successful implementation, he has consistently delivered exceptional results.
Throughout his career, he has taken on multifaceted roles, from leading technical project management teams to owning solutions that drive operational excellence. His conscientious and proactive approach is unwavering, whether he is working independently or collaboratively within a team. His ability to connect with colleagues on a personal level underscores his commitment to fostering a harmonious and productive workplace environment.
Date: May 29, 2024
Tags: Information Security, ISO/IEC 27001, ISO/IEC 42001, Artificial Intelligence, GDPR
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Training: ISO/IEC 27001 Information Security Management System - EN | PECB
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Webinars: https://pecb.com/webinars
Article: https://pecb.com/article
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How to Setup Warehouse & Location in Odoo 17 InventoryCeline George
In this slide, we'll explore how to set up warehouses and locations in Odoo 17 Inventory. This will help us manage our stock effectively, track inventory levels, and streamline warehouse operations.
Strategies for Effective Upskilling is a presentation by Chinwendu Peace in a Your Skill Boost Masterclass organisation by the Excellence Foundation for South Sudan on 08th and 09th June 2024 from 1 PM to 3 PM on each day.
LAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UPRAHUL
This Dissertation explores the particular circumstances of Mirzapur, a region located in the
core of India. Mirzapur, with its varied terrains and abundant biodiversity, offers an optimal
environment for investigating the changes in vegetation cover dynamics. Our study utilizes
advanced technologies such as GIS (Geographic Information Systems) and Remote sensing to
analyze the transformations that have taken place over the course of a decade.
The complex relationship between human activities and the environment has been the focus
of extensive research and worry. As the global community grapples with swift urbanization,
population expansion, and economic progress, the effects on natural ecosystems are becoming
more evident. A crucial element of this impact is the alteration of vegetation cover, which plays a
significant role in maintaining the ecological equilibrium of our planet.Land serves as the foundation for all human activities and provides the necessary materials for
these activities. As the most crucial natural resource, its utilization by humans results in different
'Land uses,' which are determined by both human activities and the physical characteristics of the
land.
The utilization of land is impacted by human needs and environmental factors. In countries
like India, rapid population growth and the emphasis on extensive resource exploitation can lead
to significant land degradation, adversely affecting the region's land cover.
Therefore, human intervention has significantly influenced land use patterns over many
centuries, evolving its structure over time and space. In the present era, these changes have
accelerated due to factors such as agriculture and urbanization. Information regarding land use and
cover is essential for various planning and management tasks related to the Earth's surface,
providing crucial environmental data for scientific, resource management, policy purposes, and
diverse human activities.
Accurate understanding of land use and cover is imperative for the development planning
of any area. Consequently, a wide range of professionals, including earth system scientists, land
and water managers, and urban planners, are interested in obtaining data on land use and cover
changes, conversion trends, and other related patterns. The spatial dimensions of land use and
cover support policymakers and scientists in making well-informed decisions, as alterations in
these patterns indicate shifts in economic and social conditions. Monitoring such changes with the
help of Advanced technologies like Remote Sensing and Geographic Information Systems is
crucial for coordinated efforts across different administrative levels. Advanced technologies like
Remote Sensing and Geographic Information Systems
9
Changes in vegetation cover refer to variations in the distribution, composition, and overall
structure of plant communities across different temporal and spatial scales. These changes can
occur natural.
Beyond Degrees - Empowering the Workforce in the Context of Skills-First.pptxEduSkills OECD
Iván Bornacelly, Policy Analyst at the OECD Centre for Skills, OECD, presents at the webinar 'Tackling job market gaps with a skills-first approach' on 12 June 2024
Recurrent/Metastatic HNSCC: Harnessing Immunotherapy in Comprehensive Care
1. Recurrent/Metastatic HNSCC: Harnessing
Immunotherapy in Comprehensive Care
Glenn J. Hanna, MD
Director, Center for Cancer
Therapeutic Innovation
Medical Oncologist
Center for Head & Neck Oncology
Dana-Farber Cancer Institute
Deborah Wong, MD, PhD
Associate Clinical Professor of Medicine
Division of Hematology-Oncology
UCLA Medical Center
3. Learning Objectives
HNSCC = head and neck squamous cell carcinoma.
Distinguish histopathological, molecular, and clinical biomarkers that can
inform prognosis and management of HNSCC
Assess emerging efficacy and safety data on novel agents and immune
checkpoint inhibitors for recurrent/metastatic HNSCC
Apply strategies to prevent and mitigate immune-mediated adverse events
Apply a multidisciplinary team approach to the implementation of surveillance
and survivorship care plans for patients with recurrent/metastatic HNSCC
5. KEYNOTE-048: Study Design
SCC = squamous cell carcinoma; R/M = recurrent/metastatic; ECOG = Eastern Cooperative Oncology Group; PS = performance status;
PD-L1 = programmed death-ligand 1; TPS = tumor proportional score; PFS = progression-free survival; pembro = pembrolizumab; Q3W = every 3 weeks;
AUC = area under the curve; 5-FU = 5-fluorouracil; QOL = quality of life ; Q1W = every 1 week.
Burtness et al, 2019.
First-Line Pembrolizumab for Recurrent or Metastatic HNSCC
Pembro
Pembro
plus chemo
EXTREME
Primary end points: overall survival, PFS Secondary end points: safety, tolerability, objective response, QOL
Key Eligibility Criteria
• SCC of the oropharynx, oral
cavity, hypopharynx, or larynx
• R/M disease incurable by local
therapy
• ECOG PS 0 or 1
• Tissue sample for PD-L1
assessment
• Known p16 status in the
oropharynx
Stratification Factors
• PD-L1 expression (TPS ≥50%
vs <50%)
• p16 status in oropharynx
(positive vs negative)
• ECOG PS 0 vs 1
Pembrolizumab
200 mg Q3W for up to 35 cycles
Pembrolizumab
200 mg plus carboplatin AUC 5
mg/m2 or cisplatin 100 mg/m2 plus
5-FU 1,000 mg/m2/d for 4 days for
6 cycles (every 3 weeks)
Cetuximab
400 mg/m2 loading dose, 250
mg/m2 Q1W plus carboplatin AUC
5 mg/m2 or cisplatin 100 mg/m2
plus 5-FU 1,000 mg/m2/d for 4 days
for 6 cycles
Cetuximab 250 mg/m2 Q1W
Pembrolizumab 200 mg Q3W
for up to 35 cycles total
R
A
N
D
O
M
I
Z
A
T
I
O
N
1:1:1
6. KEYNOTE-048: Overall Survival
PD-L1+ = PD-L1–positive; CPS = combined positive score; OS = overall survival; HR = hazard ratio; CI = confidence interval.
Harrington et al, 2023.
Pembrolizumab alone demonstrates improved outcomes compared with
chemotherapy-cetuximab in PD-L1+ patients
First-Line Pembrolizumab for R/M HNSCC
7. KEYNOTE-048: Overall Survival (cont.)
Harrington et al, 2023.
Pembrolizumab alone demonstrates improved outcomes compared with
chemotherapy-cetuximab in PD-L1+ patients
First-Line Pembrolizumab for R/M HNSCC
8. KEYNOTE-048: Overall Survival (cont.)
Harrington et al, 2023.
Chemoimmunotherapy improves survival in this population over platinum-
based chemotherapy with cetuximab
First-Line Pembrolizumab for R/M HNSCC
9. KEYNOTE-048: Overall Survival (cont.)
Harrington et al, 2023.
Chemoimmunotherapy improves survival in this population over platinum-
based chemotherapy with cetuximab
First-Line Pembrolizumab for R/M HNSCC
10. KEYNOTE-B10: Study Design
Dzienis et al, 2022.
First-Line Pembro/Carboplatin/Paclitaxel for R/M HNSCC
Key Eligibility Criteria
• Previously untreated R/M HNSCC of oral
cavity, oropharynx, larynx, hypopharynx
• PD-L1–agnostic
• ECOG 0-1
• Stage IVC or M1
Pembrolizumab
200 mg IV Q3W
Paclitaxel (investigator’s choice) for 6 cycles
Carboplatin AUC 5 Q3W for 6 cycles
Primary end point
• Overall response rate
Secondary end points
• Duration of response (DOR)
• Progression-free survival
• Overall survival
• Safety
11. KEYNOTE-B10: ORR and DOR per RECIST v1.1 by BICR
BICR = blinded independent central review; ORR = overall response rate; DOR = duration of response;
RECIST = Response Evaluation Criteria in Solid Tumors; carbo = carboplatin; pacli = paclitaxel; CR = complete response; PR = partial response;
SD = stable disease; PD = progressive disease; TTR = time to response; DCR = disease control rate.
Dzienis et al, 2022.
First-Line Pembro/Carboplatin/Paclitaxel for R/M HNSCC
Pembro + Carbo + Pacli
n=82
ORR, % (95% CI) 42.7% (31.8-54.1)
Best objective response, n (%)
CR 4 (4.9%)
PR 31 (37.8%)
SD 24 (29.3%)
PD 15 (18.3%)
No assessment 8 (9.8%)
TTR, median (range), months 1.5 (1.1-4.2)
DCR, % (95% CI) 58.5% (47.1-69.3)
Taxane therapy seems to yield comparable outcomes when compared with
5-FU use as part of chemoimmunotherapy
12. Novel ICI Combinations for HNSCC
ICI = immune checkpoint inhibitor; 1L = first-line; 2L = second-line; HRAS = Harvey Rat sarcoma virus; EGFR = epidermal growth factor receptor;
VEGF = vascular endothelial growth factor; STAT3 = signal transducer and activator of transcription 3; PI3K = phosphatidylinositol 3-kinase. mPFS = median PFS;
mOS = median OS.
Wise-Draper et al, 2022.
Strategies have focused on enhancing the durable benefit observed in 1L with anti–
PD-1 therapy, and on anti–PD-1 refractory patients in the 2L+ setting
Enhancing Durable Benefit in HNSCC
Class Drug or Molecule Key Findings
Phase ORR mPFS (months) mOS (months)
Targeted agents
HRAS Tipifarnib Phase 2 (30 pts) 55% 5.4 15.4
EGFR
Cetuximab/pembrolizumab Phase 2 45% - 18
Cetuximab/avelumab Phase 2 50% - -
Afatinib/pembrolizumab Phase 2 41% 4.1 8.4
VEGF
Lenvatinib/cetuximab Phase 1/2b (9/12 pts) 67% 3.6 -
Lenvatinib/pembrolizumab Phase 1/2b (22 pts) 46% 4.7 -
STAT3 Danvatirsen/durvalumab Phase 1b/2 (38 pts) 26% - -
PI3K Buparlisib vs placebo + paclitaxel Phase 2 (158 pts) 31% 4.5% 10.4%
13. Novel ICI Combinations for HNSCC (cont.)
IDO = indoleamine 2,3-dioxygenase; ICOS = anti-inducible T-cell costimulator; HPV = human papillomavirus.
Wise-Draper et al, 2022.
Class Drug or Molecule Key Findings
Phase ORR mPFS (months) mOS (months)
Other ICI combinations
IDO
Epacadostat/
pembrolizumab
Phase 2 ORR: 34%; DCR: 61% - -
Phase 2 ORR: 23%; DCR: 61% - -
Costimulatory
agents
GSK609 (ICOS agonist)/
pembrolizumab
Phase 1 26% 5.6 -
B7-H3
Enoblituzumab/
pembrolizumab
Phase 1 study (19 pts) 33% - -
NK2GA
Monalizumab/cetuximab
Phase 2
36% in immunotherapy-naive,
naive, 17% in immunotherapy-
immunotherapy- pretreated
- -
Monalizumab/cetuximab
Phase 2 study, cohort 3 33% - 15
T-cell exhaustion
exhaustion (LAG-
(LAG-3)
Eftilagimod alpha/
pembrolizumab
Phase 2 (36 pts) 36% - -
TLR-9
Intratumoral SDS-101/
pembrolizumab
Phase 1b/2
ORR: 22%
DCR: 48%
- -
TGF-beta Bintrafusp alfa Phase 1 study (32 pts)
22%, 75% had >2 prior lines of
of therapy
HPV+ group ORR 50%
- -
14. Novel ICI Combinations for HNSCC (cont.)
TIL = tumor-infiltrating lymphocytes.
Wise-Draper et al, 2022.
Class Drug or Molecule Key Findings
Phase ORR
mPFS
(months)
mOS
(months)
Cellular therapy
TIL LN-145/pembrolizumab Phase 2 study (18 pts)
ORR: 38.9%
88.9%
- -
Vaccines
Peptide/protein-based
based vaccines
ISA101b/nivolumab
Phase 2 HPV+
oropharyngeal SCC
33% - -
Nucleic acid-based
vaccines
MEDI0457/durvalumab Phase 2 22.2% - -
Oncolytic virus
Intratumoral talimogene
laherparepvec/
pembrolizumab
Phase 1b 14% 3 5.8
15. ICI + Cetuximab for R/M HNSCC
mAB = monoclonal antibody; NK = natural killer; ADCC = antibody-dependent cell-mediated cytotoxicity; PD-1 = programmed cell death protein 1;
Q2W = every 2 weeks.
Sacco et al, 2021; Chung et al, 2022; Gulati et al, 2023.
Adding an EGFR mAb to anti–PD-1 treatment offers synergistic immune
stimulation; activation of NK cells and promoting ADCC
Signal robust in HPV-negative tumors
Key Eligibility Criteria
• Platinum-resistant or platinum-ineligible HNSCC
• ≥18 years old
• ECOG 0-1
• No previous immunotherapy or EGFR inhibitor
Pembrolizumab 200 mg Q3W
Cetuximab 400 mg/m2 IV initial dose,
250 mg/m2 Q1W
Overall response rate
Cohort A: Any prior systemic therapy including
cetuximab or PD-1 inhibitors and persistent or
platinum-refractory disease
Cohort B: No prior systemic therapy
Cetuximab 500 mg/m2 Day -14 before
Cycle 1
Nivolumab 240 mg IV Q2W
Cetuximab 500 mg/m2 Q2W
Overall survival
Key Eligibility Criteria
• Metastatic HNSCC
• No prior cetuximab or immunotherapy
Durvalumab 1,500 mg IV Q4W
Cetuximab 400 mg/m2 IV initial dose,
250 mg/m2 Q1W
Overall response rate
16. Durvalumab + Cetuximab
Nivolumab + Cetuximab
Pembrolizumab + Cetuximab
Prior systemic therapy
No prior therapy
ORR: 39%
ORR: 22% Median OS: 9.6 months
Median OS:
11.4 months
ORR: 37%
Median OS: not reached
Sacco et al, 2021; Chung et al, 2022; Gulati et al, 2023.
Median OS: 18.4 months
ORR: 45%
ICI + Cetuximab for R/M HNSCC: Efficacy
17. Pembrolizumab + BCA-101 in R/M HNSCC
AE = adverse event; TGF = transforming growth factor; G2 = grade 2; G3 = grade 3; alk phos = alkaline phosphatase; AST = aspartate transaminase;
ALT = alanine transaminase.
Hanna et al, 2023a; Hanna et al, 2023b.
BCA-101: novel EGFR-TGF-beta bispecific protein
Appears safe, well-tolerated
Enhanced TGF-beta neutralization or trap to promote
immunity and augment EGFR inhibition
Signal most robust in HPV-negative tumors
Safety:
AEs of interest
Acneiform rash in 74% (7% G3)
Mucosal bleeding, generally low-grade
1 G3 related tracheal hemorrhage
AEs most commonly leading to dose interruption
4x rash, 4x anemia, 3x infusion-related reaction, 3x colitis
3/42 had dose reduction (G2 acneiform rash, G3 alk
phos/AST/ALT increased, G3 maculopapular rash)
6/42 had permanent discontinuation (2x G3 colitis, G3 alk
phos/AST/ALT increased, G3 diarrhea, G3 tracheal hemorrhage,
G4 pericarditis
Median PFS: not reached
ORR DCR
Total population 18/39 (46%) 31/39 (79%)
HPV-pos 2/11 (18%) 6/11 (55%)
CPS 1-19 0/6 (0%) 2/6 (33%)
CPS≥20 2/5 (40%) 4/5 (80%)
HPV-neg 16/28 (57%) 25/28 (89%)
CPS 1-19 7/13 (54%) 12/13 (92%)
CPS≥20 9/15 (60%) 13/15 (87%)
19. LEAP-010 and LEAP-090: Pembrolizumab + Lenvatinib
VEGFR = vascular endothelial growth factor receptor; TKI = tyrosine kinase inhibitor; IA = interim analysis.
Siu et al, 2020; Merck and Eisai, 2023.
Multitargeted VEGFR TKI to augment or rescue anti–PD-1 effects
Safety concerns with VEGFR TKIs (bleeding)
Focused on 1L and 2L patients (PD-L1+)
LEAP-010 did not meet OS endpoint in IA and was discontinued
PD-L1+ Patients with HNSCC
20. Pembrolizumab + Cabozantinib in R/M HNSCC
Saba et al, 2023.
Multitargeted VEGFR TKI to
augment anti–PD-1 effects
Toxicity seems more manageable
Focused on 1L patients (PD-L1+)
ORR: 52%
Median PFS: 14.6 months
Median OS: 22.3 months
Most Common
AEs
All
Grades
Grade
3/4
Fatigue 44.4% 0
Diarrhea 33.3% 2.8%
Hypothyroidism
m
33.3% 0
Constipation 30.6% 0
Dysphagia 19.4% 8.3%
Hypertension 25.0% 8.3%
Increased AST 11.1% 5.6%
Back pain 16.7% 5.6%
Hypotension 11.1% 5.6%
Oral mucositis 25.0% 5.6%
21. STELLAR-305: Study Design
Clinicaltrials.gov, 2023a.
Novel oral multitargeted VEGFR TKI to augment anti–PD-1 effects
Focused on 1L patients (PD-L1+)
Pembrolizumab + Zanzalintinib (XL092) for PD-L1+ R/M HNSCC
Primary end points:
overall survival, PFS
Secondary end points:
investigator-assessed PFS,
ORR, DOR
Key Eligibility Criteria
• R/M HNSCC incurable by local
therapy
• CPS ≥ 1
• ≥18 years old
• ECOG 0-1
• No prior immunotherapy or
zanzalintinib
Zanzalintinib + pembrolizumab
Placebo + pembrolizumab
R
A
N
D
O
M
I
Z
A
T
I
O
N
1:1
22. EV-202 Cohort 5: Study Design
ADC = antibody-drug conjugate.
Swiecicki et al, 2023; Clinicaltrials.gov, 2023a.
Nectin-4 targeting ADC
Demonstrates activity in platinum-/anti–PD-1–refractory HNSCC
Manageable safety profile
Now being combined with pembrolizumab in 1L PD-L1+ HNSCC cohort in EV-202
Enfortumab Vedotin for Previously Treated R/M HNC
EV-202 Cohort 5
• Locally advanced or metastatic HNC
• ECOG 0-1
• Prior platinum-based chemotherapy for
locally advanced/metastatic HNC
• Prior PD(L)-1 inhibitor or immunotherapy
contraindicated
• No more than 2 lines of chemotherapy in
the locally advanced/metastatic setting
Enfortumab vedotin 1.25 mg/kg Days 1,
8, 15 of a 28-day cycle
Primary End Point
Overall response rate
Secondary End Points
Duration of response
Disease control rate (DCR)
PFS
OS
Safety/tolerability
23. EV-202 Cohort 5: Efficacy and Safety
HNC = head and neck cancer; STD = standard deviation.
Swiecicki et al, 2023.
Median PFS: 3.94 months
Median OS: 5.98 months
ORR: 23.9%
Safety:
Common AEs were fatigue, alopecia,
peripheral neuropathy
Grade ≥3 AEs included anemia,
decreased neutrophil count,
progression of HNC
AEs of special interest: skin reactions
(45.7%), peripheral neuropathy
(32.6%), hyperglycemia (4.3%)
Enfortumab Vedotin for Previously Treated R/M HNC
24. TROPiCS-03: Study Design
Michel et al, 2023.
Trop-2–targeting ADC
Demonstrates activity in platinum and anti–PD-1 refractory HNSCC
Manageable safety profile
Sacituzumab Govitecan for R/R Metastatic or Locally Advanced HNSCC
EV-202 Cohort 5
• Locally advanced or metastatic HNC
• ECOG 0-1
• Prior platinum-based chemotherapy for
locally advanced/metastatic HNC
• Prior PD(L)-1 inhibitor or immunotherapy
contraindicated
• No more than 2 lines of chemotherapy in
the locally advanced/metastatic setting
Enfortumab vedotin 1.25 mg/kg Days
1, 8, 15 of a 28 Day cycle
Primary End Point
Overall response rate
Secondary End Points
Duration of response
DCR
PFS
OS
Safety/tolerability
25. TROPiCS-03: Efficacy and Safety
TRAE = treatment-related AE.
Michel et al, 2023.
Trop-2 targeting ADC
Demonstrates activity in
platinum-/anti–PD-1–
refractory HNSCC
Manageable safety profile
ORR: 16%
Median DOR: 4.2 months
Median PFS: 4.1 months
Sacituzumab Govitecan for R/R Metastatic or Locally Advanced HNSCC
Safety:
Any-grade AEs: 100%
Grade ≥3 AEs: 44%
TRAEs leading to discontinuation: 0
Deaths due to TRAE: 2% (1/43)
26. HPV Therapeutic Vaccines: Study Designs
HLA = human leukocyte antigen; SC = subcutaneous; IM = intramuscular.
Chung et al, 2023; Price et al, 2023; Aggarwal et al, 2023.
Variety of proprietary platforms targeting HPV16/18, some HLA-restricted
Modest activity in HPV+ R/M HNSCC alone and in combination with anti–PD-1/L1 therapies
HPV-Positive R/M HNSCC
PDS0101: VERSATILE-002
Key Eligibility Criteria
HPV16+ R/M HNSCC
Stratified by ICI-naive and ICI-refractory
Pembrolizumab IV Q3W
PDS0101 SC concurrently on Cycles 1, 2, 3, 4,
and 12 (5 doses)
End points: overall response
rate, safety PFS, OS
MEDI0457
Key Eligibility Criteria
• HPV16+ or HPV18+ R/M HNSCC
• ≥1 prior platinum chemotherapy
• No prior immunotherapy
MEDI0457 7 mg IM Day 1 of Weeks 1, 3, 7, 12
(4 doses)
Durvalumab 1,500 mg IV Day 1 of Weeks 4, 8,
12, continuing every 4 weeks
End points: overall response
rate, safety, 16-week DCR,
OS, PFS
CUE-101
Key Eligibility Criteria
• HLA-A*0201 genotype
• HPV16+ R/M HNSCC
CUE-101 Q3W
Pembrolizumab 200 mg Q3W
End points: safety,
pharmacokinetics,
pharmacodynamics, efficacy
CUE-101 Q3W
27. Efficacy of HPV Therapeutic Vaccines
Chung et al, 2023; Price et al, 2023; Aggarwal et al, 2023.
CUE-101
CUE-101 +
pembrolizumab
PDS0101 +
pembrolizumab
MEDI0457 +
durvalumab
N evaluable 19 12 34 29
ORR 1/19 (5%) 5/12 (42%) 9/34 (26.5%) 8/29 (27.6%)
Median PFS - - 10.4 months 3.5 months
Median OS 24.4 months - Not estimable 29.2 months
Safety
Fatigue, anemia, chills, infusion-related reactions,
constipation, lymphopenia, nausea
Fatigue,
injection site reactions
Fatigue,
injection site pain
HPV-Positive R/M HNSCC
28. Case Study 1: Mr. KF
R = right; BOT = base of tongue; SCC = squamous cell carcinoma; IMRT = intensity-modulated radiation therapy; fx = fractions; LRR = locoregionally recurrent;
TL = total laryngectomy; ND = neck dissection; AT = anterolateral; PEG = percutaneous endoscopic gastrostomy; TEP = tracheoesophageal puncture;
TTMV = tumor tissue–modified viral; UD = undetected; SOC = standard of care; chemoIO = chemoimmunotherapy.
62-year-old male, former smoker
T4N0, stage III, HPV18+ R BOT SCC treated with IMRT 35 fx to
70 Gy with bolus cisplatin in September 2021
LRR disease in the BOT with TL and glossectomy with NDs and
ATL flap salvage surgery in November 2023
PEG-dependent, uses TEP
December 2023: new locoregional unresectable recurrence
PD-L1 CPS 5, TTMV-HPV DNA always UD
1L SOC: pembro or chemoIO (KN-048)
1L trial option: pembro + BCA-101
29. Part 2: Prevention and
Mitigation of Immune-Related
Related Adverse Events (irAEs)
30. Toxicity of Anti–PD-1 Immunotherapy in R/M HNSCC
Ferris et al, 2016; Cohen et al, 2019; Harrington et al, 2021; Burtness et al, 2019; Rischin et al, 2022.
Treatment with nivolumab (Checkmate 141) or pembrolizumab
(KEYNOTE-040) in the 2L setting or pembrolizumab in the 1L setting
(KEYNOTE-048) is effective and well-tolerated
Most toxicities low-grade, not requiring treatment interruption or
discontinuation
Quality-of-life outcomes consistently better than with investigator’s
choice standard-of-care therapy
31. CheckMate 141: Study Design
Ferris et al, 2016.
Nivolumab for R/M HNSCC
Primary end point:
Overall survival
Secondary end points:
PFS, ORR, safety, DOR,
biomarkers, quality of life
Key Eligibility Criteria
• R/M HNSCC of the oral cavity,
pharynx, or larynx
• Within 6 months of last dose of
platinum therapy
• Known p16 status
• Tissue sample for PD-L1
assessment
Stratified by
• Prior cetuximab
Nivolumab 3 mg/kg IV Q2W
Investigator’s choice
Methotrexate 40 mg/m2 IV weekly
Docetaxel 30 mg/m2 IV weekly
Cetuximab 400 mg/m2 IV once,
then 250 mg/m2 weekly
R
A
N
D
O
M
I
Z
A
T
I
O
N
2:1
33. CheckMate 141: Adverse Events
Nivo = nivolumab.
Ferris et al, 2016.
TRAES in ≥5%
Nivo Group
Nivolumab (n=236) Standard Therapy (n=111)
Any Grade Grade 3/4 Any Grade Grade 3/4
Any event 139 (58.9%) 31 (13.1%) 86 (77.5%) 39 (35.1%)
Fatigue 33 (14.0%) 5 (2.1%) 19 (17.1%) 3 (2.7%)
Nausea 20 (8.5%) 0 23 (20.7%) 1 (0.9%)
Rash 18 (7.6%) 0 5 (4.5%) 1 (0.9%)
Decreased
appetite
17 (7.2%) 0 8 (7.2%) 0
Pruritus 17 (7.2%) 0 0 0
Diarrhea 16 (6.8%) 0 15 (13.5%) 2 (1.8%)
Anemia 12 (5.1%) 3 (1.3%) 18 (16.2%) 2 (1.8%)
Standard therapy: single-agent methotrexate, docetaxel, or cetuximab
Nivolumab for R/M HNSCC
34. KEYNOTE-040: Study Design
TTP = time to progression.
Cohen et al, 2019; Harrington et al, 2021.
Pembrolizumab for R/M HNSCC
Primary end point:
Overall survival
Secondary end points:
OS in CPS ≥1 population
PFS in all, PFS in CPS ≥1,
ORR in all, ORR in CPS
≥1, DOR in all, DOR in
CPS ≥1, TTP in all, TTP in
CPS ≥1, safety
Key Eligibility Criteria
• R/M HNSCC of the oral cavity,
oropharynx, hypopharynx, or
larynx
• Progression after platinum
regimen for R/M HNSCC or
recurrence or PD within 3-6
months of multimodal platinum
therapy
• ECOG PS 0 or 1
• Known p16 status
• Tissue sample for PD-L1
assessment
Stratified by
• ECOG PS
• p16 status
• PD-L1 TPS (≥50% vs <50%)
Pembrolizumab 200 mg IV Q3W
Investigator’s choice
Methotrexate 40 mg/m2 IV weekly
Docetaxel 30 mg/m2 IV weekly
Cetuximab 400 mg/m2 IV once,
then 250 mg/m2 weekly
R
A
N
D
O
M
I
Z
A
T
I
O
N
1:1
35. KEYNOTE-040: Quality of Life With Pembrolizumab
Cohen et al, 2019; Harrington et al, 2021.
R/M HNSCC
Time to Deterioration in QOL Change from Baseline in QOL Scores Over Time
36. KEYNOTE-040: Adverse Events With Pembrolizumab
Cohen et al, 2019; Harrington et al, 2021.
R/M HNSCC
Pembrolizumab Group (n=246) Standard-of-Care Group (n=234)
Any grade Grade 3, 4, or 5 Any grade Grade 3, 4, or 5
Treatment-related adverse event
Any event 155 (63%) 33 (13%) 196 (84%) 85 (36%)
Event leading to treatment
treatment discontinuation
15 (6%) 12 (5%) 12 (5%) 9 (4%)
Event leading to death 4 (2%) 4 (2%) 2 (1%) 2 (1%)
Event occurring in ≥5% of patients in the pembrolizumab group
Hypothyroidism 33 (13%) 1 (<1%) 2 (1%) 0
Fatigue 31 (13%) 4 (2%) 43 (18%) 2 (1%)
Diarrhea 20 (8%) 4 (2%) 24 (10%) 1 (<1%)
Rash 19 (8%) 1 (<1%) 34 (15%) 1 (<1%)
Asthenia 18 (7%) 1 (<1%) 28 (12%) 4 (2%)
Anemia 17 (7%) 1 (<1%) 33 (14%) 9 (4%)
Nausea 12 (5%) 0 29 (12%) 1 (<1%)
Event of interest occurring in ≥3% of patients in the pembrolizumab group
Any 63 (26%) 11 (4%) 28 (12%) 11 (5%)
Hypothyroidism 37 (15%) 1 (<1%) 9 (4%) 0
Pneumonitis 10 (4%) 3 (1%) 3 (1%) 3 (1%)
Infusion-related reaction 8 (3%) 1 (<1%) 7 (3%) 1 (<1%)
Severe skin reaction 7 (3%) 4 (2%) 9 (4%) 7 (3%)
37. KEYNOTE-048: Pembrolizumab for HNSCC
EORTC = European Organisation for Research and Treatment of Cancer; QLQ-C30 = Quality of Life Questionnaire–Core 30;
QLQ-H&N35 = Quality of Life Questionnaire–Head & Neck 35; TTD = time to treatment discontinuation.
Burtness et al, 2019; Rischin et al, 2022.
Health-Related Quality-of-Life Results
EORTC QLQ-C30 GHS/QOL
and QLQ-H&N35 Pain Swallowing Scores
Estimates of Time to Deterioration by Treatment
40. Toxicity of Anti–PD-1 Immunotherapy in R/M HNSCC
Burtness et al, 2019.
Serious grade 3-5 toxicities occur at a low incidence
But serious, life-threatening toxicity can occur
Close monitoring, early recognition, and intervention are key
Adverse events of
interest in ≥1%
Pembrolizumab (n=300)
Pembrolizumab-
chemotherapy (n=276)
Cetuximab-
(n=287)
Any grade Grade 3-5 Any grade Grade 3-5 Any grade Grade 3-5
Any event 93 (31%) 21 (7%) 73 (26%) 15 (5%) 68 (24%) 30 (10%)
Hypothyroidism 55 (18%) 0 44 (16%) 0 18 (6%) 0
Pneumonitis 19 (6%) 5 (2%) 15 (5%) 5 (2%) 3 (1%) 2 (<1%)
Hyperthyroidism 8 (3%) 1 (<1%) 12 (4%) 0 3 (1%) 0
Severe skin reactions 8 (3%) 6 (2%) 2 (<1%) 2 (<1%) 20 (7%) 19 (7%)
Infusion reactions 4 (1%) 2 (<1%) 6 (2%) 2 (<1%) 27 (9%) 6 (2%)
Colitis 3 (1%) 2 (<1%) 7 (3%) 2 (<1%) 2 (<1%) 2 (<1%)
Hepatitis 3 (1%) 2 (<1%) 1 (<1%) 1 (<1%) 0 0
Nephritis 3 (1%) 2 (<1%) 2 (<1%) 0 1 (<1%) 0
41. Toxicities of ICIs in Phase 3 HNSCC Studies
GI = gastrointestinal; LFT = liver function test; Cr = creatinine; CBC = complete blood count.
Haanen et al, 2022; NCCN, 2024b; Schneider et al, 2021.
Fatigue
Hypothyroidism
Skin toxicity (rash)
Decreased appetite
GI (diarrhea)
Pneumonitis
Hepatitis
Monitoring guidelines
History and physical prior to each
dose of ICI
Lab assessment:
Thyroid function tests every 4-6 weeks
LFTs, Cr, CBC prior to each dose
More frequent assessment if toxicity
develops to monitor for resolution
Early referral to specialists
42. Proposed Mechanisms of Immune Toxicity
TCR = T-cell receptor; CD = cluster of differentiation; MHC = major histocompatibility complex; CTLA = cytotoxic T-lymphocyte–associated protein;
ADCC = antibody-dependent cellular cytotoxicity; NK = natural killer; IL6 = interleukin 6.
Johnson et al, 2022; Ghisoni et al, 2021; Postow et al, 2018.
Tumor/tissue specific factors:
Common T-cell receptor sequences
upregulated transcripts in tumor and affected
normal tissue
Non-tumor specific factors:
Microbiome
Tissue specific factors
Viral factors
T-cell type
Inhibition of cytokines such as IL6
Modest correlation between response to immunotherapy and incidence of immune related
adverse events (irAEs)—most data in melanoma and lung cancer
43. General Guidelines for Management of irAEs
Haanen et al, 2022; NCCN, 2024b; Schneider et al, 2021.
Grade 1
Continue ICI with close monitoring
Grade 2
Hold ICI until resolution to grade ≤1
Consider corticosteroids (prednisone 0.5-1 mg/kg/day or equivalent)
Grade 3:
Hold ICI
Initiate high-dose steroids (prednisone 1-2 mg/kg/day or equivalent), tapering over 4-6 weeks
Cases refractory to steroids may require other immunosuppressants/biologics
Grade 4
High-dose steroids, permanent discontinuation of ICI
Organ-specific exceptions
Endocrinopathies—hormone replacement and can continue ICI if corrected
Grade 2 dermatologic toxicity can be managed with topical steroids and emollients while continuing
ICI
44. Case Study 2: Ms. MC
SOB = shortness of breath.
65-year-old woman with metastatic HNSCC, former smoker
Initially presented with T3N1 SCC oral cavity
Resection adjuvant chemo-RT
At 1 year post-resection, develops lung metastases
Lung biopsy: SCC, PD-L1 CPS 5
Chemoimmunotherapy with carboplatin/5FU + pembrolizumab x4 cycles
Maintenance pembrolizumab x2 months
Develops cough, SOB
Improves somewhat with antibiotics
45. Case Study 2: Ms. MC (cont.)
CT chest
Interval decreased size of left upper lobe lung mass
New/increased airspace consolidations of the right upper lobe and
right lower lobe lung fields
Constellation of findings is most concerning for organizing
pneumonia in the setting of drug toxicity, although infectious
pneumonia cannot be excluded
Right upper lung transbronchial biopsy
Intra-alveolar fibrin deposition with focal increased eosinophils,
neutrophils, reactive pneumocyte hyperplasia
Acid-fast (AFB) and Methenamine silver (GMS) stain negative for
organisms
Negative for carcinoma
Comment: the biopsy shows a nonspecific pattern of acute lung
injury with intra-alveolar fibrin and an increase in eosinophils and
neutrophils. The differential diagnosis includes drug reaction,
eosinophilic pneumonia, and infectious etiologies
46. Case Study 2: Ms. MC
Prednisone 1 mg/kg followed by slow taper
Follow-up CT chest 3 months later
Stable left upper lobe, mass-like consolidation
Improved airspace opacities
Remains in continued response off therapy
47. Future Directions: Areas of Need
Ghisoni et al, 2021; Johnson et al, 2022.
Most studies on toxicity and QOL focus on short-term follow-up
CheckMate 141 and KEYNOTE-040 primarily reported data at Week 15 therapy
Anticipated dropoff of subjects completing QOL questionnaires after 15 weeks
Ghisoni et al reported of 56 publications of ICI registration trials, 90.3% did not report
duration of irAEs or data on patients experiencing ongoing irAEs at data cutoff (median
23.5% patients on ongoing treatment, range 1%-63%)
More common long-term toxicities: endocrinopathies, arthralgias/inflammatory arthritis
Management guidelines for emerging combination therapy given overlapping
toxicity
Dermatologic toxicity with combined ICI with anti-EGFR directed therapies
Diarrhea, hepatotoxicity, mucositis with combined ICI with anti-VEGFR therapies
48. Part 3: Clinical and Molecular
Biomarkers in Advanced HNSCC
HNSCC to Inform Management
49. Biomarkers of HNSCC: HPV
EBV = Epstein-Barr virus.
Fakhry et al, 2014.
One of our most important prognostic biomarkers even in the setting of
R/M disease
Despite this, we treat HPV-positive (HPV+) and -negative R/M HNSCC
similarly for now (with some caveats)
EBV is another example of a viral biomarker
50. Biomarkers: Circulating Tumor DNA (ctDNA)
Aulakh et al, 2022.
Powerful tool to monitor disease status and response
Several commercial assays available
Some platforms are tumor-informed
51. Biomarkers for HNSCC: HPV (ct)DNA
Rettig et al, 2022.
TTMV-HPV DNA
Baseline detectability and levels correlate with nodal burden
Not all cases are detectable at baseline (could be prognostic)
52. Biomarkers for HNSCC: HPV (ct)DNA (cont.)
PPV = positive predictive value; NPV = negative predictive value.
Hanna et al, 2023; Berger et al, 2022.
TTMV-HPV DNA
Powerful tool to monitor disease status in surveillance
High PPV and NPV among large retrospective series
Prospective data emerging
53. Biomarkers for HNSCC: PD-L1 Status
Haddad et al, 2022.
Inflammatory biomarkers may predict response to anti–PD-1 therapy in R/M HNSCC
KEYNOTE-012: nonrandomized phase 1b trial of pembrolizumab 10 mg/kg IV Q2W or
pembrolizumab 200 mg Q3W for patients with HNSCC with or without PD-L1 expression
KEYNOTE-012
54. KEYNOTE-048: PD-L1 Status as a Biomarker
RR = response rate.
Burtness et al, 2019.
Inflammatory biomarkers do seem to predict
response to anti-PD-1 therapy in R/M
HNSCC
KEYNOTE-048: pembro vs pembro/chemo
vs cetuximab/chemo
43% of patients had PD-L1 CPS ≥20
With pembro vs cetuximab/chemotherapy:
Improved OS: 14.9 vs 10.7 months
Lower RR: 23% vs 36%
With pembro/chemo vs
cetuximab/chemotherapy:
Improved OS: 14.7 vs 11.0 months
Similar RR: 43% vs 38%
Pembrolizumab for R/M HNSCC
55. Biomarkers for HNSCC: TMB
TMB = tumor mutational burden; tTMB = tissue TMB.
Wildsmith et al, 2023.
TMB also seems to predict response to anti–PD-1/L1 therapy in R/M HNSCC
Phase 2 HAWK and CONDOR and phase 3 EAGLE studies of durvalumab with or
without tremelimumab in platinum-resistant R/M HNSCC
HAWK, CONDOR, and EAGLE Trials
Durvalumab Durvalumab/tremelimumab Durvalumab
56. Biomarkers for HNSCC: TMB (cont.)
Haddad et al, 2022.
KEYNOTE-012: Pembro for R/M HNSCC
TMB also seems to predict response to anti–PD-1/L1 therapy in R/M HNSCC
KEYNOTE-012: nonrandomized phase 1b trial of pembro 10 mg/kg IV Q2W or pembro 200 mg
Q3W for patients with HNSCC with or without PD-L1 expression
57. Biomarkers for HNSCC: HRAS Mutations
VAF = high variant allele frequency.
Ho et al, 2021; Ho et al, 2023; Coleman et al, 2023; Hanna et al, 2022; Patel et al, 2023.
Proto-oncogene present in 4% to 8% of R/M HNSCC
Tipifarnib, a farnesyl transferase inhibitor (FTI), has demonstrated good safety and
antitumor activity, particularly among high VAF patients
Ongoing KURRENT trial combining tipifarnib with the PI3K pathway inhibitor
alpelisib in this population
Novel oral FTI (KO-2806) in clinical development
PR
SD
58. Biomarkers for HNSCC: PIK3CA Mutations
PIK3CA = phosphatidylinositol-4,5-bisphosphonate 3-kinase catalytic subunit alpha.
Hanna et al, 2018; Geiger et al, 2016; Razak et al, 2023.
PI3KCA pathway important, particularly in HPV+ disease
May be associated with improved outcomes in the R/M setting
Cohort of 42 patients with metastatic HPV+
oropharyngeal cancer, 16 (38%) with PI3K
pathway mutations
Patients with PI3K pathway mutations had
significantly improved survival
59. Biomarkers for HNSCC: PIK3CA Mutations
mTOR = mammalian target of rapamycin.
Hanna et al, 2018; Geiger et al, 2016; Razak et al, 2023.
Trials have explored mTOR inhibition (everolimus), PIK3CA/EGFR inhibition
(alpelisib/cetuximab), etc
Everolimus and Alpelisib/Cetuximab
Everolimus Alpelisib/cetuximab vs cetuximab alone Alpelisib/cetuximab
n=71
ORR: 9.9%
DCR:43.7%
mPFS = 2.9 months
No advantage over
cetuximab alone
7 of 9 evaluable
ORR: 0
DCR: 28%
mPFS: 1.5 months
mOS: 4.5 months
33% discontinued due to toxicity
60. Case Study 3: Ms. JP
CUP = cancer of unknown primary; PR = partial response; PD = progressive disease; NGS = next-generation sequencing;
AKT2 = serine/threonine protein kinase 2; MS = microsatellite; mut = mutation.
65-year-old female, never-smoker
TXN2M1, stage IV, HPV16+ CUP treated with 1L chemoimmunotherapy
(platinum-taxane with pembrolizumab) through November 2021 (7 months) with
PR
At PD, in January 2022 started 2L protocol therapy on KURRENT trial
(tipifarnib/alpelisib)
PD-L1 CPS 80, TTMV-HPV DNA+
NGS: MS-stable, TMB 1 mut/Mb, AKT2 amplified, PIK3CA amplified, PIK3CA
E545K hotspot mutation
1L SOC: pembro + chemo
2L: trial of tipifarnib/alpelisib
63. Multidisciplinary Care in Head and Neck Cancer
RT = radiotherapy.
Chow, 2020; Mody et al, 2021; Friedland et al, 2011; Licitra et al, 2016; Pillay et al, 2016.
Essential throughout the patient journey from initial diagnosis to survivorship
Best outcomes in patients treated at high-volume centers with
multidisciplinary team
Most R/M HNSCC patients are diagnosed with locally advanced disease
Locally advanced HNSCC requires multimodal therapy:
Surgery adjuvant RT ± chemotherapy, definitive chemo-RT
Treatment goals balance best oncologic outcome with morbidity, minimizing
short- and long-term toxicity, and considerations of other factors that impact
care
64. Components of a Multidisciplinary Head and Neck Team
Chow, 2020; Mody et al, 2021; Friedland et al, 2011; Licitra et al, 2016; NCCN, 2024a; Pillay et al, 2016.
Surgeons
Surgical oncologist
Neurosurgeons
Plastic surgeons
Oral maxillofacial surgeon
Radiation oncologists
Medical oncologists
Palliative care
Pathologists
Radiologists
Clinical nutrition
Maxillofacial prosthetics
Dentists
Physical therapists
Occupational therapists
Speech language therapists
Audiologists
Nurses
Psychologists
Social workers
65. Post-Treatment Surveillance of HNSCC
NCCN, 2024a.
Approximately 50% of patients with locally advanced HNSCC will
develop R/M HNSCC
Annual incidence of second primary cancers is 3%-7%
Early detection of recurrence or second primary may improve prognosis
Allows identification of other long-term complications of treatment that
impact quality of life, function, and survival outcomes
66. Post-Treatment Surveillance of HNSCC (cont.)
TSH = thyroid-stimulating hormone; T4 = thyroxine; IGF-2 = insulin-like growth factor 2; LH = luteinizing hormone; FSH = follicle-stimulating hormone;
ACTH = adrenocorticotropic hormone; CT = computed tomography; MRI = magnetic resonance imaging; PET/CT = positron emission tomography/CT.
NCCN, 2024a; Machiels et al, 2020; Nekhylyudov et al, 2017.
History and physical exam
Most recurrences within 2
years of treatment
Head and neck exam and
mirror and fiberoptic exam
Year 1: every 1-3 months
Year 2: every 2-6 months
Year 3-5: every 4-8 months
Annually after Year 5
Lab evaluation
If neck radiation: TSH every 6-12 months
If skull base radiation: annual evaluation for
panhypopituitarism (AM cortisol, growth
hormone, free T4, IGF-2, LH, FSH, ACTH,
TSH, testosterone)
Consider HPV DNA, EBV DNA if virally-
mediated HNC
Imaging
CT or MRI 3-4 months post surgery
PET/CT 3-6 months after definitive radiation
or chemoradiotherapy
Additional imaging thereafter for equivocal
findings or symptoms
67. Post-Treatment Surveillance of HNSCC (cont.)
NCCN, 2024a; Machiels et al, 2020; Nekhylyudov et al, 2017.
Dental evaluation
Every 6 months if radiation
Supportive care and rehabilitation
Speech and swallow for dysphagia
Physical therapy/rehab for trismus, cervical dystonia, muscle spasms, shoulder
dysfunction
Audiology
Lymphedema management
Nutrition
Smoking cessation
Screening for depression and distress management
68. Long-Term Complications in R/M HNSCC
Brauer 2022; Kuhn et al, 2023.
Psychosocial distress
60% of head and neck cancer patients report versus 40% of cancer patients
Treatment-related side effects, functional impairment, disfigurement, persistent pain,
fatigue
Distressed HNC patients have poorer outcomes: treatment delay, poor compliance,
longer hospitalizations, poorer quality of life and survival
Dysphagia
New symptoms should prompt workup for recurrence or second primary
Lifelong monitoring
Nutritional status, weight as surrogate indicators of dysphagia
Poor nutrition
Chronic pain due to dystonia, neuropathy, trismus, fibrosis
Fatigue: assess for endocrinopathies
69. Multidisciplinary Management of R/M HNSCC
In the context of locoregional relapse RM HNSCC, multimodal treatment
with salvage surgery, re-irradiation, ablation, systemic therapy is utilized
Utility of salvage surgery: curative intent, locoregional control, palliation of
symptoms
Re-irradiation
Consolidation local therapy or palliative re-RT
Long-term toxicity of immunotherapy-based regimens may require
multidisciplinary management of chronic irAEs
Riaz et al, 2014; Roland & Bradley, 2014.
70. Chronic irAEs From Immune Checkpoint Inhibition
irAEs persisting >12 weeks after discontinuation of anti–
PD-L1 treatment
Limited data, mostly retrospective
43.2% of patients
Most common long-term toxicities
Hypothyroidism
Diabetes mellitus type I
Inflammatory arthritis
Less common but reported: dermatologic toxicity,
neuropathy, pneumonitis
Mechanisms
Irreversible damage to cells (endocrinopathies, vitiligo)
Waxing/waning off-target T-cell activation—smoldering
toxicity (inflammatory arthritis, dermatologic toxicity)
Johnson et al, 2022.
Dermatitis/eczema Vitiligo
71. Case Study 4: Ms. CS
s/p = status post; L = left; FNA = fine needle aspiration; PET = positron emission tomography.
34-year-old woman, never-smoker with a painful lesion on the left lateral
oral tongue
pT2pN2bM0 SCC left oral tongue
s/p L hemiglossectomy, left selective neck dissection
Adjuvant chemoradiation 60 Gy with weekly cisplatin
8 months later, palpated lesion left lower neck
FNA + SCC
PET/CT imaging: isolated enlarged PET-avid left supraclavicular lymph node no distant
metastatic disease
Salvage surgery: left revision neck dissection
Adjuvant re-irradiation
4 months later noted increasing left neck and sternal pain
72. Case Study 4: Ms. CS (cont.)
FDG = fluorodeoxyglucose; mets = metastases.
PET/CT
Intense FDG uptake in left level II-IV
neck soft tissue, likely combination of
post treatment changes and recurrent
tumor
FDG avid lymph nodes left neck
supraclavicular, paratracheal, internal
mammary and axillary
Large lytic destructive soft tissue mass
centered in the manubrium compatible
with osseous metastasis
Additional bone mets at C5 and the left
first rib
73. Case Study 4: Ms. CS
Treated with cetuximab + pembrolizumab
Pain resolved 6 weeks into treatment
PET/CT at 3 months
Interval improvement in disease in neck soft tissues
Decrease in size and resolution of FDG avidity
manubrium soft tissue mass: 30 x26 14 x 8 mm
Cetuximab discontinued after 5 months for
grade 2 acneiform rash, paronychia
Pembrolizumab monotherapy continued
Baseline
3 months on cetuximab + pembrolizumab
74. Case Study 4: Ms. CS (cont.)
NSAID = nonsteroidal anti-inflammatory agent.
13 months into treatment
Swelling and pain in left knee and bilateral hands
NSAIDs
Partially improves with prednisone but recurs with discontinuing steroids
Referred to rheumatology
Joint injections
NSAIDs
Prednisone
Hydroxychloroquine
Pembrolizumab discontinued after 13 months of therapy
Remains off therapy >2 years
Last PET/CT
Manubrial lesion 30 x26 14 x 8 mm 5x4 mm, no FDG uptake
Persistent waxing / waning arthritis, continues hydroxychloroquine,
NSAIDs, low-dose prednisone (as needed)
75. Key Takeaways
Investigational therapies in R/M disease are currently focused on
novel immunotherapeutic combinations, ADCs, and EGFR-directed
therapies
Tumor NGS and PD-L1 CPS should be performed on all R/M patients
at the onset of advanced disease
HPV remains an important prognostic biomarker even in the R/M
setting
76. Key Takeaways (cont.)
Treatment with ICIs improves quality of life compared with palliative
chemotherapy or targeted therapy
Toxicity is low in most cases
Corticosteroids are the mainstay of treatment for serious immune-
related adverse events
Multidisciplinary care from initial diagnosis to survivorship is essential
for head and neck cancer patients
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Notas do Editor
ADD data showing study schema/design, ORR with safety and median PFS/OS