AOCNP Immunotherapy and Targeted Therapy 2 — Questions and Answers
Question 1: Which of the following is a CTLA-4 checkpoint inhibitor used in the treatment of melanoma?
- Nivolumab
- Pembrolizumab
- Ipilimumab (Correct answer)
- Atezolizumab
Correct answer: Ipilimumab
Ipilimumab (Yervoy) is a monoclonal antibody that blocks CTLA-4, an inhibitory receptor on T cells that normally downregulates immune responses. It was the first checkpoint inhibitor approved (2011) for unresectable or metastatic melanoma.
Question 2: A patient with ALK-rearranged NSCLC who progresses on crizotinib should be switched to which next-generation ALK inhibitor?
- Erlotinib
- Alectinib or brigatinib (Correct answer)
- Osimertinib
- Larotrectinib
Correct answer: Alectinib or brigatinib
Alectinib, brigatinib, and lorlatinib are second/third-generation ALK inhibitors with activity against crizotinib-resistant mutations and superior CNS penetration. Alectinib and brigatinib are now preferred as first-line therapy due to their superior efficacy over crizotinib.
Question 3: The ONCP/NP monitoring for immune-related colitis from checkpoint inhibitors should include which key assessment?
- Serum creatinine and BUN levels only
- Stool frequency, consistency, presence of blood, and abdominal examination (Correct answer)
- Complete blood count and differential
- Thyroid function tests only
Correct answer: Stool frequency, consistency, presence of blood, and abdominal examination
Immune-related colitis typically presents as diarrhea (>4 stools/day above baseline), abdominal pain, or hematochezia. Systematic assessment of stool frequency, blood/mucus, abdominal cramping, and hydration status guides grading and management decisions for irAE colitis.
Question 4: PARP inhibitors such as olaparib are most effective in patients with which molecular feature?
- High tumor mutational burden (TMB-H)
- BRCA1/2 or other homologous recombination repair (HRR) deficiency (Correct answer)
- MSI-high status
- EGFR exon 19 deletion
Correct answer: BRCA1/2 or other homologous recombination repair (HRR) deficiency
PARP inhibitors exploit synthetic lethality in tumors with HRR deficiency, most commonly BRCA1/2 mutations. When BRCA-mutated cells cannot repair double-strand breaks via HRR, PARP inhibition prevents base excision repair, leading to catastrophic DNA damage and cell death.
Question 5: Which VEGF/VEGFR-targeted agent is associated with the highest risk of gastrointestinal perforation and arterial thromboembolism?
- Trastuzumab
- Bevacizumab (Correct answer)
- Cetuximab
- Rituximab
Correct answer: Bevacizumab
Bevacizumab (anti-VEGF monoclonal antibody) is associated with unique class-specific toxicities including GI perforation (1–2%), arterial thromboembolism, wound healing impairment, hypertension, and proteinuria. Patients must be monitored closely for these complications.
Question 6: Tumor mutational burden (TMB) is used as a biomarker for which type of immunotherapy response prediction?
- Response to PARP inhibitors
- Response to checkpoint inhibitors (Correct answer)
- Response to HER2-targeted therapy
- Response to anti-VEGF therapy
Correct answer: Response to checkpoint inhibitors
High TMB (TMB-H, ≥10 mutations/megabase) is associated with greater neoantigen burden, making tumors more visible to the immune system. Pembrolizumab received FDA approval for TMB-H solid tumors regardless of histology, establishing TMB as a predictive biomarker for checkpoint inhibitor response.
AOCNP Immunotherapy and Targeted Therapy 2
Which of the following is a CTLA-4 checkpoint inhibitor used in the treatment of melanoma?