Immunotherapy and Targeted Therapy Flashcards

Which class of immunotherapy works by blocking the PD-1/PD-L1 checkpoint pathway to restore anti-tumor T-cell activity?

Answer: Checkpoint inhibitors

Checkpoint inhibitors such as pembrolizumab (anti-PD-1), nivolumab (anti-PD-1), and atezolizumab (anti-PD-L1) block inhibitory signals that tumor cells use to suppress T-cell activity, thereby restoring the immune system's ability to recognize and destroy cancer cells.

Imatinib (Gleevec) is a tyrosine kinase inhibitor (TKI) that targets which molecular abnormality in chronic myelogenous leukemia (CML)?

Answer: BCR-ABL fusion protein

Imatinib specifically inhibits the BCR-ABL tyrosine kinase produced by the Philadelphia chromosome (t(9;22) translocation) in CML. It was the first targeted therapy to demonstrate that molecular targeting of a cancer driver mutation could produce durable remissions.

A patient receiving pembrolizumab develops severe, grade 3 immune-related pneumonitis. What is the most appropriate initial management?

Answer: Permanently discontinue pembrolizumab and start high-dose corticosteroids

Grade 3–4 immune-related pneumonitis requires permanent discontinuation of the checkpoint inhibitor and initiation of high-dose systemic corticosteroids (prednisone 1–2 mg/kg/day or methylprednisolone IV), with pulmonology consultation. This is a potentially life-threatening irAE.

Which biomarker must be tested before initiating trastuzumab (Herceptin) therapy for breast cancer?

Answer: HER2 overexpression or gene amplification

Trastuzumab targets the HER2 (human epidermal growth factor receptor 2) protein. HER2 testing by IHC (3+ overexpression) and/or FISH/ISH (gene amplification) is mandatory before initiating trastuzumab, as it is only effective in HER2-positive tumors (~15–20% of breast cancers).

Cytokine release syndrome (CRS) is a potentially life-threatening toxicity most commonly associated with which type of immunotherapy?

Answer: CAR-T cell therapy and bispecific T-cell engagers

CRS occurs when large numbers of immune cells are activated and release excessive cytokines (especially IL-6, IFN-γ), causing fever, hypotension, and hypoxia. It is most severe with CAR-T therapies (e.g., tisagenlecleucel) and bispecific T-cell engagers (e.g., blinatumomab). Tocilizumab is the treatment of choice for severe CRS.

EGFR-mutated non-small cell lung cancer (NSCLC) is most effectively treated with which class of targeted agents?

Answer: EGFR tyrosine kinase inhibitors (e.g., osimertinib)

EGFR TKIs, particularly third-generation osimertinib, are first-line standard of care for EGFR-mutated (exon 19 deletion or L858R) NSCLC. Osimertinib also covers T790M resistance mutations and has better CNS penetration compared to first/second-generation TKIs.