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2026
1. A 65-year-old woman with metastatic non-small cell lung cancer (NSCLC) is
being evaluated for targeted therapy. Next-generation sequencing of her tumor
biopsy reveals an exon 19 deletion in the EGFR gene. Which agent would be the
MOST appropriate first-line targeted therapy?
a) Crizotinib
b) Osimertinib
c) Dabrafenib
d) Bevacizumab
- answer: B) Osimertinib
• Rationale: For NSCLC with EGFR sensitizing mutations (exon 19 deletions
or L858R point mutation), third-generation EGFR TKIs like osimertinib are
now first-line standard of care due to superior CNS penetration and efficacy
against T790M resistance mutations. Crizotinib (A) is for ALK-rearranged
NSCLC. Dabrafenib (C) is for BRAF V600E mutations. Bevacizumab (D) is an
anti-VEGF antibody used in combination therapy but not specifically for
EGFR mutations.
2. A patient with HER2-positive metastatic breast cancer develops disease
progression after treatment with trastuzumab, pertuzumab, and docetaxel.
Which agent would be MOST appropriate for next-line therapy, considering its
unique mechanism of action and indication for HER2-positive metastatic breast
cancer after prior anti-HER2 therapy?
a) Lapatinib plus capecitabine
b) Ado-trastuzumab emtansine (T-DM1)
,c) Trastuzumab deruxtecan (T-DXd)
d) Everolimus plus exemestane
- answer: C) Trastuzumab deruxtecan (T-DXd)
• Rationale: T-DXd is a HER2-directed antibody-drug conjugate with a
topoisomerase I inhibitor payload. It is indicated for HER2-positive
metastatic breast cancer after prior anti-HER2 therapy (including T-DM1)
and has shown superior efficacy compared to T-DM1 (B) in this setting. T-
DM1 is typically used after progression on trastuzumab + taxane in the
metastatic setting, but after progression on T-DM1, T-DXd is preferred.
Lapatinib (A) is an older option. Everolimus (D) is for hormone receptor-
positive, HER2-negative disease.
3. A patient with metastatic colorectal cancer (CRC) with wild-type RAS and
BRAF genes is being considered for first-line therapy with an EGFR inhibitor.
Which statement regarding anti-EGFR therapy in CRC is CORRECT?
a) Cetuximab and panitumumab are equally effective in tumors with KRAS or
NRAS mutations.
b) Anti-EGFR therapy should only be used in combination with bevacizumab for
maximal effect.
c) Response to anti-EGFR therapy is limited to tumors with wild-type RAS (KRAS
and NRAS) genes.
d) The primary dose-limiting toxicity is cardiac dysfunction requiring serial MUGA
scans.
- answer: C) Response to anti-EGFR therapy is limited to tumors with wild-type
RAS (KRAS and NRAS) genes.
• Rationale: Anti-EGFR monoclonal antibodies (cetuximab, panitumumab)
are ONLY effective in metastatic CRC that is wild-type for KRAS and NRAS
exon 2, 3, and 4 mutations. Mutations in these genes constitutively
activate the pathway downstream of EGFR, making EGFR blockade
ineffective. They are not used with bevacizumab (B) concurrently due to
increased toxicity and no survival benefit. The primary toxicities are
dermatologic (acneiform rash) and hypomagnesemia, not cardiac (D).
, 4. A patient with advanced renal cell carcinoma (RCC) with a history of
myocardial infarction and stable angina is being evaluated for first-line systemic
therapy. Which class of targeted therapy should generally be AVOIDED in this
patient due to its cardiovascular risk profile?
a) mTOR inhibitors (e.g., everolimus)
b) VEGF receptor tyrosine kinase inhibitors (e.g., sunitinib, pazopanib)
c) Immune checkpoint inhibitors (e.g., nivolumab + ipilimumab)
d) HIF-2α inhibitors (e.g., belzutifan)
- answer: B) VEGF receptor tyrosine kinase inhibitors (e.g., sunitinib, pazopanib)
• Rationale: VEGF TKIs (sunitinib, pazopanib, axitinib) are associated
with significant cardiovascular toxicities, including hypertension (nearly
universal), left ventricular dysfunction, heart failure, and QT prolongation.
In a patient with established coronary artery disease and prior MI, these
agents pose a high risk. Immune checkpoint inhibitors (C) can cause
myocarditis but it is less common. mTOR inhibitors (A) have metabolic
effects. HIF-2α inhibitors (D) are newer agents with different toxicity
profiles.
5. A patient with chronic-phase chronic myeloid leukemia (CML) is started on
imatinib but develops a BCR-ABL1 T315I mutation at 12 months, indicating
resistance. Which agent is specifically indicated for T315I-mutated CML?
a) Nilotinib
b) Dasatinib
c) Bosutinib
d) Ponatinib
- answer: D) Ponatinib
• Rationale: The T315I "gatekeeper" mutation confers resistance to all first-
and second-generation BCR-ABL1 TKIs (imatinib, nilotinib, dasatinib,
bosutinib). Ponatinib is a third-generation TKI specifically designed to bind
BCR-ABL1 with the T315I mutation and is the primary therapeutic option,
though it carries significant risks of arterial thrombosis and vascular events.
Section 2: Immuno-Oncology & CAR-T Therapy