1.
ODACon™ Supportive Care Summit:
Managing Toxicities of Novel Breast Cancer Therapies
k
HER2 Tyrosine Kinase Inhibitors
Abbey Kaler, MS, APRN, FNP-C
Advanced Practice Registered Nurse
University of Texas
MD Anderson Cancer Center

2.
Disclosures
Advisory board/panel: AstraZeneca
Speaker’s bureau: Novartis, Sanofi Genzyme
i3 Health has mitigated all relevant financial relationships

3.
Learning Objectives
HER2 = human epidermal growth factor receptor 2.
Assess the indications and safety and efficacy profiles of HER2
tyrosine kinase inhibitors for breast cancer
Evaluate clinical tools for assessing and grading adverse events
associated with novel HER2 tyrosine kinase inhibitors
Apply strategies to optimize safety and tolerability of novel HER2
tyrosine kinase inhibitors
Develop educational strategies to help patients understand the
benefits and risks of their breast cancer treatment plan

4.
HER2-Positive Diagnosis
CEP17 = centromeric region of chromosome 17.
Marchiò et al, 2021; BreastCancer.org, 2022.
HER2 Expression by Immunohistochemistry (IHC)
Score 0 Score 1+
HER2-Negative HER2-Positive
HER2-Borderline
HER2-Positive
HER2-Negative
HER2 Expression by Fluorescence in Situ Hybridization (FISH)
Red: HER2
Green: CEP17
Score 2+ Score 3+
IHC score 1+
or
IHC score 2+
plus negative FISH
HER2-Low

5.
HER2 Tyrosine Kinase: Definition
ACS, 2022b; Iancu et al, 2022; MyCancerGenome®, 2016.
Human epidermal growth factor receptor 2
(HER2 or also called ERBB2) is a type of
protein known as a kinase
Tyrosine kinases phosphorylate specific amino
acids on substrate enzymes
Kinases send signals to the cell to grow and
divide
They alter signal transduction, leading to
downstream changes to modify cell growth,
migration, differentiation, apoptosis, and death

6.
HER2 Tyrosine Kinase: Definition (cont.)
TKI = tyrosine kinase inhibitor.
ACS, 2022b; Iancu et al, 2022; MyCancerGenome®, 2016.
Drugs that block kinases are
called kinase inhibitors
Blocking these initial signals via TKIs
can prevent the aberrant action of the
mutated or dysfunctional TKs
2 classes of drugs that block HER2
signaling
Monoclonal antibodies: extracellular
Small molecules: intracellular

7.
HER2 TKIs: Background
TK = tyrosine kinase; EGFR = epidermal growth factor receptor.
Image from PDB entry 1XKK courtesy of Fvasconcellos.
Iancu et al, 2022; Pottier et al, 2020; ACS, 2022a.
Over 50 TKIs FDA-approved for cancer
Bladder
Breast
Gastrointestinal (GI)
Leukemia
Lung
Lymphoma
Melanoma
Renal cell
Thyroid
Anti-EGFR TKIs used in breast cancer
HER2 is a member of the EGFR family
HER2 overexpression in ~20% of breast cancer
Lapatinib
EGFR/HER2/HER4 inhibitor

8.
HER2 TKIs FDA-Approved for Breast Cancer
ACS, 2022b; Dent et al, 2021; Pottier et al, 2020.
Lapatinib: reversible inhibitor of
HER1 and HER2, first approval in
2007
Neratinib: irreversible (covalent)
pan-HER (HER1, HER2, and
HER4) inhibitor, first approval in
2017
Tucatinib: reversible, selective
HER2 inhibitor with low affinity for
EGFR, first approval in 2020

9.
HER2 TKIs Approved for Breast Cancer (cont.)
ACS, 2022b.
Lapatinib
Pill taken daily
Used to treat advanced breast cancer
Typically given along with trastuzumab and the chemo drug capecitabine
Neratinib
Pill taken daily
Used to treat early-stage breast cancer after treatment with trastuzumab for 1 year;
usually given for 1 year
Can also be given along with the chemo drug capecitabine to treat metastatic disease,
typically after ≥2 other anti-HER2 targeted drugs
Tucatinib
Pill, typically taken twice a day
Used to treat advanced breast cancer after ≥1 prior HER-targeted drug
Usually given along with trastuzumab and the chemo drug capecitabine

10.
HER2 TKIs:
Safety and Efficacy in
Clinical Trials

11.
NALA: Neratinib for Metastatic Breast Cancer
PFS = progression-free survival; CNS = central nervous system.
Saura et al, 2020.
Neratinib + capecitabine vs lapatinib + capecitabine
Patients with HER2-positive metastatic breast cancer and
≥2 prior HER2 therapies for metastatic breast cancer
Median PFS: 8.8 months with neratinib, 6.6 months with
lapatinib
Median OS: 24.0 months with neratinib, 22.2 months with
lapatinib
Included patients with asymptomatic or stable brain
metastases
Fewer patients in the neratinib + capecitabine group required
interventions for CNS metastases vs lapatinib + capecitabine
(22.8% vs 29.2%), suggesting prevention of or delayed time to
development of CNS disease
After ≥2 Previous HER2-Directed Therapies
HR-negative
HR-positive

12.
ExteNET: Neratinib for Early Breast Cancer
HR = hormone receptor; OS = overall survival.
Chan et al, 2021.
Phase 3 randomized controlled trial
2,840 patients with HER2-positive early breast cancer after neoadjuvant/adjuvant
trastuzumab-based therapy
Neratinib significantly improved invasive disease-free survival (iDFS) in the HER2-
positive/HR-positive population who initiated treatment ≤1 year after trastuzumab
(≤1 year). A similar trend was observed in patients who had residual disease after
neoadjuvant treatment
iDFS at 5 years was 5.1% in HR-positive/≤1-year patients and 1.3% in HR-positive/
>1-year patients
Improvements in central nervous system events and OS were consistent with iDFS
benefits, suggesting long-term benefit for neratinib in this population
In HR-positive/≤1-year patients, neratinib had a numerical improvement in OS at
8 years
HER2-Positive Early Breast Cancer

13.
ExteNET: Neratinib (cont.)
Intention-to-treat population
HER2-positive/HR-positive early-stage
breast cancer within 1 year of prior
trastuzumab
Patients with residual disease after
neoadjuvant therapy
1,334 patients
HER2-positive/HR-positive early-stage breast
cancer within 1 year of prior trastuzumab
295 patients
HER2-positive/HR-positive early-stage breast
cancer within 1 year of prior trastuzumab with
residual disease after neoadjuvant therapy
Invasive disease-
free survival
5-year follow-up
Overall survival
8-years follow-up
Absolute benefit 5.1%
for neratinib vs placebo
Absolute benefit 2.1%
for neratinib vs placebo
Absolute benefit 7.4%
for neratinib vs placebo
Absolute benefit 9.1%
for neratinib vs placebo
Chan et al, 2021.
2,840 patients
HER2+ early-stage breast cancer after
trastuzumab

14.
ExteNET: Neratinib for Breast Cancer (cont.)
Chan et al, 2021.
Safety: HR-Positive/≤1 Year Population
Neratinib (n=662) Placebo (n=657)
Any treatment-emergent adverse event (TEAE)
(TEAE)
649 (98%) 587 (86%)
Grade 3/4 TEAE 327 (49%) 76 (12%)
Fatal TEAE 1 (<1%) 0
TEAE leading to dose reduction 203 (31%) 13 (2%)
TEAE leading to treatment discontinuation 178 (27%) 30 (5%)
Grade 1-2 Grade 3 Grade 1-2 Grade 3
Diarrhea 365 (55%) 261 (39%) 219 (32%) 7 (1%)
Nausea 280 (42%) 9 (1%) 135 (21%) 2 (<1%)
Fatigue 177 (27%) 13 (2%) 129 (20%) 2 (<1%)
Vomiting 150 (23%) 24 (4%) 41 (6%) 2 (<1%)
Abdominal pain 145 (22%) 11 (2%) 58 (9%) 1 (<1%)
Headache 119 (18%) 6 (<1%) 125 (19%) 1 (<1%)
Upper abdominal pain 90 (14%) 6 (<1%) 35 (5%) 3 (<1%)
Rash 90 (14%) 3 (<1%) 40 (6%) 0
Decreased appetite 79 (12%) 1 (<1%) 13 (2%) 0
Muscle spasms 81 (12%) 0 21 (3%) 1 (<1%)

15.
HER2CLIMB: Tucatinib/Trastuzumab/Capecitabine
Murthy et al, 2020; Curigliano et al, 2022.
Phase 3 randomized controlled trial
612 patients with HER2-positive metastatic breast cancer previously treated
with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not
have brain metastases
Progression-free survival at 1 year:
33.1% in the tucatinib combination group
12.3% in the placebo combination group
Median duration of progression-free survival:
7.8 months in the tucatinib combination group
5.6 months in the placebo combination group
Overall survival at 2 years:
44.9% in the tucatinib-combination group
26.6% in the placebo-combination group
HER2-Positive Metastatic Breast Cancer

16.
HER2CLIMB: Tucatinib/Trastuzumab/Capecitabine (cont.)
Curigliano et al, 2022.
Final Analysis: Progression-Free Survival

17.
HER2CLIMB: Tucatinib/Trastuzumab/Capecitabine (cont.)
Curigliano et al, 2022.
Final Analysis: Overall Survival
Particularly notable survival
outcomes, as nearly half of
patients enrolled in
HER2CLIMB had brain
metastases, including
patients who had active
brain metastases at
baseline

18.
Murthy et al, 2020; Le Du et al, 2021.
Progression-Free Survival for Patients With Brain Metastases
HER2CLIMB: Tucatinib/Trastuzumab/Capecitabine (cont.)
First large randomized
trial to include patients
with metastatic breast
cancer and active brain
metastases, and the first
to demonstrate a
significant impact on
central nervous system
(CNS) disease by adding
a systemic therapy

19.
AE = adverse event; PPE = palmar-plantar erythrodysesthesia.
Murthy et al, 2020; Curigliano et al, 2022.
Safety
HER2CLIMB: Tucatinib/Trastuzumab/Capecitabine (cont.)
Event Tucatinib-Combination Group (n=404) Placebo-Combination Group (n=197)
Any grade Grade ≥3 Any grade Grade ≥3
Any AE 401 (99.3%) 245 (60.6%) 191 (97.0%) 101 (51.3%)
Diarrhea 331 (81.9%) 53 (13.1%) 106 (53.8%) 17 (8.6%)
PPE syndrome 264 (65.3%) 57 (14.1%) 105 (53.3%) 18 (9.1%)
Nausea 243 (60.1%) 16 (4.0%) 88 (44.7%) 7 (3.6%)
Fatigue 193 (47.8%) 22 (5.4%) 87 (44.2%) 8 (4.1%)
Vomiting 152 (37.6%) 13 (3.2%) 51 (25.9%) 8 (4.1%)
Stomatitis 105 (26.0%) 10 (2.5%) 28 (14.2%) 1 (0.5%)
Decreased appetite 105 (26.0%) 3 (0.7%) 41 (20.8%) 0
Headache 96 (23.8%) 3 (0.7%) 40 (20.3%) 3 (1.5%)
Aspartate aminotransferase increased
increased
89 (22.0%) 19 (4.7%) 22 (11.2%) 1 (0.5%)
Alanine aminotransferase increased 81 (20.0%) 23 (5.7%) 13 (6.6%) 1 (0.5%)
Anemia 88 (21.8%) 17 (4.2%) 24 (12.2%) 5 (2.5%)
Blood bilirubin increased 81 (20.0%) 4 (1.0%) 21 (10.7%) 5 (2.5%)

20.
HER2 TKIs:
Adverse Events

21.
Side Effects of HER2 TKIs for Breast Cancer
Tykerb® prescribing information, 2022; Nerlynx® prescribing information, 2022; Tukysa® prescribing information, 2022.
Lapatinib Neratinib Tucatinib
Boxed warning: hepatotoxicity
Heart failure
Interstitial lung disease
Prolonged QT interval
Embryotoxicity
Diarrhea
Hand-foot syndrome
Nausea
Vomiting
Fatigue
Diarrhea
Hepatotoxicity
Embryotoxicity
Nausea
Abdominal pain and distention
Vomiting
Rash
Stomatitis
Muscle spasms
Skin and nail disorder
Diarrhea
Hepatotoxicity
Embryotoxic
Hand-foot syndrome
Nausea
Fatigue
Stomatitis
Abdominal pain
Headache
Anemia

22.
Monitoring for HER2 TKIs in Breast Cancer
Iancu et al, 2022; Dent et al, 2021; Nerlynx® prescribing information, 2022; Tykerb® prescribing information, 2022.
Echocardiogram or multigated blood-pool imaging (MUGA) and
electrolyte monitoring; left ventricular ejection fraction monitoring
(lapatinib)
Liver enzyme panels

23.
Cardiac Toxicity: Lapatinib
QTc = corrected QT interval.
NCI, 2017.
HER2 TKIs for Breast Cancer
Cardiac event Grade 1 Grade 2 Grade 3 Grade 4 Grade 5
Heart failure
Asymptomatic with
laboratory (eg, brain
natriuretic peptide) or
or cardiac imaging
abnormalities
Symptoms with mild-to-
moderate activity or exertion
Severe with symptoms at
at rest or with minimal
activity/exertion, or
intervention indicated
Life-threatening consequences, or
or urgent intervention indicated (eg,
(eg, continuous intravenous
therapy or mechanical
hemodynamic support)
Death
QT prolongation
prolongation
QTc 450-480 ms QTc 481-500 ms
Average QTc ≥501 ms or
>60-ms change from
baseline
Torsades de Pointes, or
polymorphic ventricular
tachycardia, or signs of symptoms
symptoms of serious arrhythmia
—

24.
QTc Prolongation: Lapatinib
Giudicessi et al, 2019; Kim et al, 2021.
Normal patient interval <440 ms
Definition: QT interval prolongation
>450 ms in males
>460 ms in females
Risk factors:
Advanced age
Renal and hepatic dysfunction
Multi-comorbidities
Polypharmacy
Electrolyte imbalances from nausea, vomiting, diarrhea, decreased oral
intake
HER2 TKIs for Breast Cancer

25.
Management of QTc Prolongation
ECG = electrocardiogram.
Tykerb® prescribing information, 2022; Kim et al, 2021; Chemocare.com, 2022.
ECG should be assessed before initiating the treatment and should be
monitored regularly depending on risk level
Electrolyte abnormalities (especially potassium and magnesium) should be
corrected before the start of treatment
Ask patients to immediately report palpitations and shortness of
breath
HER2 TKIs for Breast Cancer

26.
Assessing and Grading Adverse Events: Liver Toxicity
ULN = upper limit of normal; GGT = gamma-glutamyl transferase; DILI = drug-induced liver injury; ADL = activities of daily living.
NCI, 2017.
Adverse event Grade 1 Grade 2 Grade 3 Grade 4 Grade 5
Alkaline phosphatase
phosphatase
increased
>ULN–2.5x ULN if baseline was
was normal, or 2-2.5x baseline if
if baseline was abnormal
>2.5–5x ULN if baseline was
normal, or >2.5-5x baseline if
baseline was abnormal
>5-20x ULN if baseline was
normal, or >5-20x baseline if
baseline was abnormal
>20x ULN if baseline was
normal, or >20x baseline if
baseline was abnormal
-
Alanine
aminotransferase
increased
>ULN–3x ULN if baseline was
normal, or 1.5-3x baseline if
baseline was abnormal
>3-5x ULN if baseline was
normal, or >3-5x baseline if
baseline was abnormal
>5-20x ULN if baseline was
normal, or >5-20x baseline if
baseline was abnormal
>20x ULN if baseline was
normal, or >20x baseline if
baseline was abnormal
-
Aspartate
aminotransferase
increased
>ULN–3x ULN if baseline was
normal, or 1.5-3x baseline if
baseline was abnormal
>3-5x ULN if baseline was
normal, or >3-5x baseline if
baseline was abnormal
>5-20x ULN if baseline was
normal, or >5-20x baseline if
baseline was abnormal
>20x ULN if baseline was
normal, or >20x baseline if
baseline was abnormal
-
Blood bilirubin
increased
>ULN–1.5x ULN if baseline was
was normal, or >1-1.5x baseline
baseline if baseline was
abnormal
>1.5-3x ULN if baseline was
normal, or >1.5-3x baseline if
baseline was abnormal
>3-10x ULN if baseline was
normal, or >3-10x baseline if
baseline was abnormal
>10x ULN if baseline was
normal, or >10x baseline if
baseline was abnormal
-
GGT increased
>ULN–2.5x ULN if baseline was
was normal, or 2-2.5x baseline if
if baseline was abnormal
>2.5-5x ULN if baseline was
normal, or >2.5-5x baseline if
baseline was abnormal
>5-20x ULN if baseline was
normal, or >5-20x baseline if
baseline was abnormal
>20x ULN if baseline was
normal, or >20x baseline if
baseline was abnormal
-
Hepatic failure - -
Asterixis, or mild
encephalopathy, or drug-
induced liver injury (DILI), or
limiting self-care ADL
Life-threatening consequences,
consequences, or moderate-to-
to-severe encephalopathy,
or coma
Death
Portal hypertension - Decreased portal vein flow
Reversal/retrograde portal vein
vein flow associated with
varices and/or ascites
Life-threatening consequences,
consequences, or urgent
intervention needed
Death

27.
Management of Liver Toxicity
LFT = liver function test.
Tykerb® prescribing information, 2022; Nerlynx® prescribing information, 2022; Tukysa® prescribing information, 2022; Le Du et al, 2021.
LFT monitoring before start of treatment and regularly afterwards, and
as indicated
Lapatinib: every 4-6 weeks
Neratinib: monthly for the first 3 months, then every 3 months
Tucatinib: every 3 weeks
Hepatotoxicity may occur days to months after starting treatment and
may be asymptomatic, so monitoring is critical
Management: hold dose until improvement and/or reduce dose;
permanent discontinuation for severe liver impairment
HER2 TKIs for Breast Cancer

28.
Diarrhea
NCI = National Cancer Institute; CTCAE = Common Terminology Criteria for Adverse Events.
NCI, 2017.
NCI CTCAE v5.0 Diarrhea
Adverse
event
Grade 1 Grade 2 Grade 3 Grade 4 Grade 5
Diarrhea
Increase of <4
stools per day over
over baseline, or
mild increase in
ostomy output
compared with
baseline
Increase of 4-6 stools
per day over baseline,
baseline, or moderate
moderate increase in
ostomy output
compared with
baseline, or limiting
instrumental ADL
Increase of ≥7 stools per
per day over baseline, or
or hospitalization
indicated, or severe
increase in ostomy output
output compared with
baseline, or limiting self-
self-care ADL
Life-threatening
consequences,
or urgent
intervention
indicated
Death

29.
Management of Diarrhea
Tykerb® prescribing information, 2022; Nerlynx® prescribing information, 2022; Tukysa® prescribing information, 2022; Le Du et al, 2021.
Management of diarrhea should be proactive
Special guidance for neratinib: initiate loperamide with first dose of neratinib
and continue loperamide for 2 cycles (56 days), then use loperamide as
needed to maintain 1-2 bowel movements per day
Or 2-week neratinib dose escalation with antidiarrheals added as indicated
For all HER2 TKIs
Grade 1, 2, and 3: start or adjust antidiarrheals, make dietary modifications,
maintain fluid intake
Grade 3 or grade 1 or 2 with complicating features: interrupt dosing, consider
dose reduction upon restarting treatment when diarrhea resolves to grade ≤1
Grade 4: permanently discontinue
HER2 TKIs for Breast Cancer

30.
Hand-Foot Syndrome
Kwakman et al, 2022; BreastCancer.org, 2022b.
Occurs when drug leaks out of capillaries on palms of hands/soles of feet
Lateral parts/distal fat pads of palms usually affected before soles of feet
Symptoms
Numbness
Itching, tingling, or burning sensation
Redness
In patients with skin of color, may present as macular hyperpigmentation instead of redness
Swelling
Discomfort
Tenderness
Rash
Flaking, cracked, or peeling skin
Blisters, ulcers, or sores
Intense pain
Difficulty walking or using hands
Palmar-Plantar Erythrodysesthesia Syndrome

31.
Hand-Foot Syndrome (cont.)
ADL = activities of daily living; WHO = World Health Organization; NCI = National Cancer Institute.
Kwakman et al, 2022; NCI 2017.
Grading
Grade 1 Grade 2 Grade 3 Grade 4
WHO
Dysesthesia/paresthesia,
tingling in hands and feet
Discomfort in walking and/or in
in holding objects, painless
swelling, redness
Painful swelling and
redness in palms and
soles, and around
fingernails and toes
Scaling, ulceration,
blistering,
severe pain
NCI
Minimal skin changes or
dermatitis (redness,
swelling, hyperkeratosis)
without pain
Skin changes (peeling, blisters,
blisters, bleeding, fissures,
swelling, hyperkeratosis) with
pain, limiting instrumental ADL
ADL
Severe skin changes
(peeling, blisters, bleeding,
bleeding, fissures, swelling,
swelling, hyperkeratosis)
with pain, limiting self-care
care ADL
-
Grading for
patients of color
on capecitabine
therapy
Hyperpigmentation of
palms and soles
Thickening of skin and palms
and soles, with pain and loss of
of function
Ulceration, dermatitis,
or scaling
-

32.
Hand-Foot Syndrome (cont.)
Kwakman et al, 2022; BreastCancer.org, 2022b.
In week following treatment
Avoid prolonged heat exposure on hands and feet
Avoid hot water
Keep pressure off hands and feet
Avoid massages or rubbing hands and feet
Don’t use tools like screwdrivers, hammers, gardening tools,
and knives (chopping)
Limit exercise involving running and jumping
Patient Education About Prevention

33.
Hand-Foot Syndrome (cont.)
Kwakman et al, 2022; BreastCancer.org, 2022b.
Apply ice packs wrapped in a towel
Elevate hands and feet whenever sitting or lying down
Pat skin dry; don’t rub dry
Pat mild skin cream into skin to keep it moist
Wear loose and ventilated shoes; don’t wear tight shoes or shoes that
rub
Stay away from harsh chemicals like laundry detergent or cleaning
supplies
Management

34.
Oral Medications and Adherence
OTC = over-the-counter.
Iancu et al, 2022; Nerlynx® prescribing information, 2022.
Unique dosing for each medication and patient
Many factors can contribute to reduced potency and the development of
acquired resistance
Whether or not food intake affects bioavailability
Mechanism of drug metabolism and elimination
Liver and kidney function
Presence of other medications that alter stomach pH
Patient demographics
Drug-to-drug interactions
OTC medications (including antacids with neratinib)
Herbal supplements
Vitamins
Foods including grapefruit (lapatinib and neratinib)
HER2 TKIs for Breast Cancer

35.
Patient Education
s/s = signs/symptoms.
Chemocare.com, 2022.
Adherence to prescribed treatment regimen
Management of side effects:
Cardiac toxicity
Communicate urgent s/s to clinical team
Liver toxicity
Diarrhea
Drug-to-drug interactions
HER2 TKIs for Breast Cancer

36.
Case Study: Ms. TY
DCIS = ductal carcinoma in situ; ER = estrogen receptor; PR = progesterone receptor; TPH = docetaxel/trastuzumab/pertuzumab;
TP = trastuzumab/pertuzumab.
2014
Left breast 5-mm DCIS, grade 2, left segmental mastectomy,
1-mm margins
Left axillary dissection, 15 negative lymph nodes
Radiotherapy
Declined adjuvant endocrine
2017
New metastatic disease to the bone and lymph nodes
ER 60% positive, PR 60% positive, HER2-amplified by FISH
(ratio 5.30)
TPH x4 months (docetaxel dropped after 4 months due to toxicity)
TP + tamoxifen + zoledronic acid

37.
Case Study: Ms. TY
MRI = magnetic resonance imaging.
2021
Headaches
MRI brain: 4.1-cm right frontal metastasis, 0.9-cm left cerebellar lesion,
0.6-cm ring-enhancing focus
Right frontal lobe craniotomy, ER 0%, PR 0%, HER2 3+
Gamma knife to cerebellar lesion
Tucatinib, capecitabine, and trastuzumab

38.
Case Study: Ms. TY (cont.)
Why was Ms. TY started on tucatinib/capecitabine/trastuzumab and
not trastuzumab emtansine as second-line therapy in the metastatic
setting?
a. Time since original diagnosis
b. New brain metastasis
c. Only completed 4 cycles of TPH
d. Prior metastasis to bone and lymph

39.
Case Study: Ms. TY (cont.)
Why was Ms. TY started on tucatinib/capecitabine/trastuzumab and
not trastuzumab emtansine as second-line therapy in the metastatic
setting?
a. Time since original diagnosis
b. New brain metastasis
c. Only completed 4 cycles of TPH
d. Prior metastasis to bone and lymph

40.
Key Takeaways
HER2 is a protein kinase, overexpressed on the cell surface of ~20% of
breast cancers, that sends signals to grow and divide
TKIs target these cancer cells while causing less damage to normal cells
HER2 TKIs have improved survival for HER2-positive breast cancer
Particularly in patients with brain metastases
Potentially serious s/s:
Congestive heart failure
QT interval prolongation
LFT elevations
Diarrhea
Oral medication adherence is key!

41.
Thank you!
Abbey Kaler, MS, APRN, FNP-C
acjeansonne@mdanderson.org
@AbbeyKaler

42.
References
American Cancer Society (2022a). Breast cancer facts and figures 2022-2024. Available at: https://www.cancer.org/research/cancer-facts-statistics/breast-cancer-facts-figures.html
American Cancer Society (2022b). Targeted drug therapy for breast cancer. Available: https://www.cancer.org/cancer/breast-cancer/treatment/targeted-therapy-for-breast-cancer.html
BreastCancer.org (2022). What are anti-HER2 therapies? Available at: https://www.breastcancer.org/treatment/targeted-therapy/what-are-anti-her2-therapies
Chan A, Moy B, Mansi J, Ejlertsen B, et al (2021). Final efficacy results of neratinib in HER2-positive hormone receptor-positive early-stage breast cancer from the phase III ExteNET trial. Clin
Breast Cancer, 21(1):80-91.e7. DOI:10.1016/j.clbc.2020.09.014
Chemocare.com (2022). Lapatinib. Available at: https://chemocare.com/chemotherapy/drug-info/lapitinib.aspx
Curigliano G, Mueller V, Borges V et al (2022). Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without
brain metastases (HER2CLIMB): final overall survival analysis. Ann Oncol, 33(3):321-329. DOI:10.1016/j.annonc.2021.12.005
Dent SF, Morse A, Burnette S, et al (2021). Cardiovascular toxicity of novel HER2-targeted therapies in the treatment of breast cancer. Curr Oncol Rep, 23(11):128. DOI:10.1007/s11912-021-
01114-x
Giudicessi JR, Noseworthy PA & Ackerman MJ (2019). The QT interval. Circulation, 139(24):2711-2713. DOI:10.1161/CIRCULATIONAHA.119.039598
Iancu G, Serban D, Badiu CD, et al (2022). Tyrosine kinase inhibitors in breast cancer (Review). Spandidos Pub, 23(2), 114. DOI:10.3892/etm.2021.11037
Kim PY, Irizarry-Caro JA, Ramesh T, et al (2021). How to diagnose and manage QT prolongation in cancer patients. JACC CardioOncol, 3(1):145-149. DOI:10.1016/j.jaccao.2021.01.002
Le Du F, Diéras V & Curigliano G (2021). The role of tyrosine kinase inhibitors in the treatment of HER2+ metastatic breast cancer. Euro J Cancer, 154:175-189. DOI:10.1016/j.ejca.2021.06.026
Marchiò C, Annaratone L, Marques A, et al (2021). Evolving concepts in HER2 evaluation in breast cancer: Heterogeneity, HER2-low carcinomas and beyond. Semin Cancer Biol, 72:123-135.
DOI:10.1016/j.semcancer.2020.02.016
Murthy RK, Loi S, Okines A, et al (2020). Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med, 13;382(7):597-609. DOI:10.1056/NEJMoa1914609
MyCancerGenome® (2016). Receptor tyrosine kinase/growth factor signaling. Available at: https://www.mycancergenome.org/content/pathways/receptor-tyrosine-kinase-growth-factor-signaling/
National Cancer Institute (2017). Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Available at:
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf
Nerlynx® (neratinib) prescribing information (2022). Puma Biotechnology. Available at: https://nerlynxhcp.com/pdf/full-prescribing-information.pdf

43.
References (cont.)
Pottier C, Fresnais M, Gilon M, et al (2020). Tyrosine kinase inhibitors in cancer: breakthrough and challenges of targeted therapy. Cancers (Basel), 12(3):731. DOI:10.3390/cancers12030731
National Cancer Institute (2017). Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Available at:
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf
Saura C, Oliveira M, Feng YH, et al (2020). Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with ≥2 HER2-directed
regimens: phase III NALA trial. J Clin Oncol, 38(27):3138-3149. DOI:10.1200/JCO.20.00147
Tukysa® (tucatinib) prescribing information (2022). Seagen. Available at: https://www.tukysahcp.com/pdf/TUKYSA_Full_Ltr_Master.pdf
Tykerb® (lapatinib) prescribing information (2022). GlaxoSmithKline. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022059s007lbl.pdf
Yang X, Wu D, Yuan S (2020). Tyrosine kinase inhibitors in the combination therapy of HER2 positive breast cancer. Technol Cancer Res Treat, 19:1533033820962140.
DOI:10.1177/1533033820962140