Hans Hammers, MD, PhD, Tri Le, MD, and patient Robert Wilonsky prepared useful practice aids pertaining to RCC for this CME/MOC/CNE/CPE activity titled "Finding the Path to Clinically Meaningful Outcomes Among Expanding Treatment Options in Renal Cell Carcinoma." For the full presentation, monograph, complete CME/MOC/CNE/CPE information, and to apply for credit, please visit us at https://bit.ly/3aRrKzu.CME/MOC/CNE/CPE credit will be available until June 12, 2021.

1. Access the activity, “Finding the Path to Clinically Meaningful Outcomes Among
Expanding Treatment Options in Renal Cell Carcinoma,” at PeerView.com/KSB40
IMDC: International Metastatic Renal Cell Carcinoma Database Consortium; LLN: lower limit of normal; mOS: median overall survival; MSKCC: Memorial Sloan Kettering Cancer Center;
RCC: renal cell carcinoma; ULN: upper limit of normal.
1. https://www.mdcalc.com. 2. Heng DY et al. J Clin Oncol. 2009;27:5794-5799. 3. Motzer RJ et al. J Clin Oncol. 2002;20:289-296. 4. NCCN Clinical Practice Guidelines in Oncology: Kidney Cancer.
Version 2.2020. https://www.nccn.org/professionals/physician_gls/PDF/kidney.pdf.
PRACTICE AID
Criteria for Evaluating Risk
in RCC: Risk Calculators1-4
Guidance From IMDC and MSKCC: Know Your Risk
IMDC Risk Model
for Metastatic RCC
MSKCC Risk Model
for Metastatic RCC
Prognostic Factor Yes No
Diagnosis to systemic treatment
interval <1 y
£ £
Karnofsky Performance Status
<80%
£ £
Hemoglobin <LLN
(Normal: 120 g/L or 12 g/dL)
£ £
Corrected serum calcium >ULN
(Normal: 8.5-10.2 mg/dL)
£ £
Neutrophils >ULN
(Normal: 2.0-7.0 x 109
/L)
£ £
Platelets >ULN
(Normal: 150,000-400,000 cells/mcL)
£ £
No. of Factors Risk Group mOS
0 Favorable 43.2 mo
1-2 Intermediate 22.5 mo
3-6 Poor 7.8 mo
No. of Factors Risk Group mOS
0 Favorable 20 mo
1-2 Intermediate 10 mo
3-5 Poor 4 mo
Prognostic Factor Yes No
Diagnosis to systemic treatment
interval <1 y
£ £
Karnofsky Performance Status
<80%
£ £
Hemoglobin <LLN
(Normal, men: 13.5-17.5 g/dL;
women: 12.0-15.5 g/dL)
£ £
Corrected serum calcium
>10 mg/dL
£ £
Lactate dehydrogenase x
ULN >1.5
(Normal: 140 U/L)
£ £
Calculating risk score is important
for treatment decisions; multiple risk
criteria are available

2. Access the activity, “Finding the Path to Clinically Meaningful Outcomes Among
Expanding Treatment Options in Renal Cell Carcinoma,” at PeerView.com/KSB40
1. https://kccure.org/. 2. https://clinicaltrials.gov/ct2/show/NCT03141177. 3. https://www.urotoday.com/recent-abstracts/urologic-oncology/renal-cancer/120904-phase-3-checkmate-9er-trial-
evaluating-opdivo-nivolumab-in-combination-with-cabometyx-cabozantinib-in-previously-untreated-advanced-renal-cell-carcinoma-demonstrates-positive-results.html.
PRACTICE AID
Kidney Cancer Resources for
Patients and Caregivers
Kidney Cancer Treatment Options
Have you been diagnosed with metastatic
or advanced kidney cancer? The US FDA has
approved 14 therapies for the treatment of
metastatic kidney cancer and one adjuvant
therapy for high-risk localized kidney cancer
following surgery. The following table lists
the three combinations approved for
advanced kidney cancer treatment in the
frontline setting; please see this section of
the website for information on all 14 options.
Kidney Cancer Types
This page describes the different
types of kidney cancer. The most
common form of cancer found in
the kidney is renal cell carcinoma
(RCC), but there are different
subtypes. A pathologist identifies
these subtypes or histologies by
looking at your tumor tissue under a microscope
following surgery or a biopsy. Knowing your
subtype is important because it could impact
decisions about surveillance and treatment.
Generic
Names
How It
Works
FDA
Approval
Mainly
Used
Ipilimumab +
nivolumab
Dual
immunotherapy:
anti–CTLA-4
inhibitor/
anti–PD-1
checkpoint inhibitor;
infusion
In 2018, for
intermediate-
and high-risk
metastatic
RCC
1st
line
Pembrolizumab
+ axitinib
Immunotherapy
(anti–PD-1
checkpointinhibitor)
+ targeted therapy
(tyrosine kinase
inhibitor); infusion
and oral
In 2019,
for metastatic
RCC
1st
line
Avelumab +
axitinib
Immunotherapy
(anti–PD-L1
checkpointinhibitor)
+ targeted therapy
(tyrosine kinase
inhibitor); infusion
and oral
In 2019,
for metastatic
RCC
1st
line
The Kidney Cancer Research Alliance (KCCure)1
provides answers to questions that patients and caregivers are asking.
Wherever they are in their diagnosis, patients can visit kccure.org to find updated information on different types of kidney
cancer, new treatment options, and more.
Clear cell
Translocation
Collectingduct
~70% of RCC
3-4% of RCC
<3% of RCC
Papillary
Unclassified
Clearcellpapillary
~10-15% of RCC
3-4% of RCC
<3% of RCC
Chromophobe
Renal medullary
Cystic
~5% of RCC
Rare
2.5% of RCC
Stay
Up to
Date!
CheckMate -9ER2,3
(cabozantinib + nivolumab)
reported positive results;
data will be out soon.
CHECKMATE-214KEYNOTE-426JAVELIN101

3. Access the activity, “Finding the Path to Clinically Meaningful Outcomes Among
Expanding Treatment Options in Renal Cell Carcinoma,” at PeerView.com/KSB40
PRACTICE AID
Guide to Managing Adverse
Events Associated With Immune
Checkpoint Inhibitors and TKIs1,2
• In general, checkpoint inhibitor therapy should be continued with close monitoring,
with the exception of some neurologic, hematologic, and cardiac toxicities
Minimal or no symptoms; diagnostic changes only
Grade 1
• Hold checkpoint inhibitor therapy for most grade 2 toxicities
• Consider resuming immunotherapy when symptoms and/or laboratory values
revert to grade 1 or lower
• Corticosteroids (initial dose of 0.5-1 mg/kg/d of prednisone or equivalent) may
be administered
Grade 3 toxicities:
• Hold checkpoint inhibitor therapy
• Initiate high-dose corticosteroids (prednisone 1-2 mg/kg/d or methylprednisolone
IV 1-2 mg/kg/d)
• If symptoms do not improve with 48-72 hours of high-dose corticosteroids,
infliximab may be offered for some toxicities
• Taper corticosteroids over the course of at least 4-6 weeks
• When symptoms and/or laboratory values revert to grade 1 or lower, rechallenging
with immunotherapy may be offered; however, caution is advised, especially in
those patients with early-onset irAEs. Dose adjustments are not recommended
Grade 4 toxicities:
• In general, permanent discontinuation of checkpoint inhibitor therapy is warranted,
with the exception of endocrinopathies that have been controlled by hormone
replacement
Grade 2
Mild to moderate symptoms
Severe or life-threatening symptoms
Grades 3/4
Immune checkpoint inhibitors are associated with important
clinical benefits, but general immunologic enhancement can also
lead to a unique spectrum of immune-related adverse events (irAEs)
irAEs are often diagnosed by
exclusion; other causes should
be ruled out (including AEs of
other therapies used), but
immunotherapy-related
toxicity should always be
included in the differential
There should be a high level of
suspicion that new symptoms
are treatment related; early
recognition, evaluation, and
treatment of irAEs plus patient
education are essential for best
outcome
Depending on severity of
irAEs, management may
require corticosteroid or other
immunosuppressive
treatment as well as
interruption or
discontinuation of therapy
If appropriate,
immunosuppressive treatment
is used; patients generally
recover from irAEs
How should irAEs be diagnosed
and managed?
What are the general recommendations
for management?
What is the spectrum of potential irAEs?
Pancreatitis,
autoimmune diabetes
Colitis
Enteritis
Encephalitis, aseptic meningitis
Thyroiditis, hypothyroidism,
hyperthyroidism
Dry mouth, mucositis
Hypophysitis
Uveitis
Pneumonitis
Thrombocytopenia,
anemia
Hepatitis
Adrenal insufficiency
Nephritis
Vasculitis
Arthralgia
Neuropathy
Rash, vitiligo
Myocarditis
Any organ system can be affected; commonly occurring are pulmonary
(pneumonitis), dermatologic (rash, pruritus, blisters, ulcers, vitiligo),
gastrointestinal (diarrhea, enterocolitis, transaminitis, hepatitis, pancreatitis),
and endocrine (thyroiditis, hypophysitis, adrenal insufficiency) irAEsWhy do
irAEs occur?
“Taking the brakes off”
of the immune system can
help the body fight cancer,
but it can also lead to toxicity
from a“supercharged”
immune system.

4. Access the activity, “Finding the Path to Clinically Meaningful Outcomes Among
Expanding Treatment Options in Renal Cell Carcinoma,” at PeerView.com/KSB40
PRACTICE AID
Guide to Managing Adverse
Events Associated With Immune
Checkpoint Inhibitors and TKIs1,2
ADL: activities of daily living; AMS: altered mental status; HFSR: hand–foot skin reaction; IO: immunotherapy; irAE: immune-related adverse event; PRES: posterior reversible encephalopathy
syndrome; TKI: tyrosine kinase inhibitors.
1. Postow MA et al. N Engl J Med. 2018;378:158-168. 2. Brahmer JR et al. J Clin Oncol. 2018;36:1714-1768. 3. Walko CM et al. Semin Oncol. 2014;41(suppl 2):s17-s28. 4. CTCAE version 5.0.
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50. 5. McLellan B et al. Ann Oncol. 2015;26:2017-2026. 6. Brose MS et al. Semin Oncol. 2014;41(suppl 2):s1-s16.
7. Lacouture ME et al. Oncologist. 2008;13:1001-1011. 8. https://www.urotoday.com/conference-highlights/asco-gu-2020/asco-gu-2020-kidney-cancer/119282-asco-gu-2020-toxicity-profiles-
and-side-effect-management-of-first-line-treatment-options-of-renal-cell-carcinoma.html.
Common adverse events associated with TKIs include
diarrhea, fatigue, and hand−foot skin reaction3,4
 Monitor bowel habits, and report any increase
in activity above normal
 Avoid spicy or fatty foods; plain, simple foods
are best
 Avoid fruit and caffeine
 Maintain adequate fluid intake to avoid
dehydration
 Monitor/manage electrolytes
 Loperamide is usually effective
 If loperamide is ineffective, consider
diphenoxylate/atropine
Diarrhea4
Hand–Foot Skin Reaction5-7
For frequent, watery, bloody, or nocturnal stools,
or any diarrhea or abdominal distress, patients
should notify medical team immediately.
Fatigue4
IO + TKI Combination Toxicities8
Educating your patients on managing fatigue
is essential.
Be aware of overlapping toxicities that can occur
with IO + TKI combination therapy.
Patient Education
 Staying as active as possible helps regulate sleep
 Maintain a normal work and social schedule
 Take breaks as needed
 Tell your medical team if activity is intolerable or
fatigue worsens
 Erythema with or without blisters;
hyperkeratotic lesions on palms and soles
 Commonly accompanied by dysesthesia
(burning, pain, tingling)
 Perform full-body skin examination, focusing
on deformities and hyperkeratotic areas on
palms and soles, before treatment initiation
 Have patients remove their shoes and examine
their feet during each visit
 Recommend podiatrist evaluation (can help with
removal of calluses and hyperkeratotic regions)
and orthotist evaluation and use of orthotic
devices in patients with abnormal weight bearing
 During early therapy (2-4 wk), encourage rest
and avoidance of vigorous exercise and
traumatic activity
Medical Intervention
General Management
Symptoms
Prophylaxis
Immunotherapy VEGF TKI
Pruritus
Pneumonitis
Myocarditis
Adrenal crisis
Hypertension
Taste changes
Stomatitis
Dyspepsia
Cytopenias
HFSR
Rash
Diarrhea
Hepatitis
Hypothyroid
AMS
Encephalitis PRES