Immunotherapy and Targeted Therapy Flashcards

Which of the following is a CTLA-4 checkpoint inhibitor used in the treatment of melanoma?

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.

A patient with ALK-rearranged NSCLC who progresses on crizotinib should be switched to which next-generation ALK inhibitor?

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.

The ONCP/NP monitoring for immune-related colitis from checkpoint inhibitors should include which key assessment?

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.

PARP inhibitors such as olaparib are most effective in patients with which molecular feature?

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.

Which VEGF/VEGFR-targeted agent is associated with the highest risk of gastrointestinal perforation and arterial thromboembolism?

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.

Tumor mutational burden (TMB) is used as a biomarker for which type of immunotherapy response prediction?

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.