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HER2+ Cholangiocarcinoma — SCE Medical Oncology MCQ

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HardGI CancersHER2+ CholangiocarcinomaSCE Medical Oncology

A patient with previously treated HER2-positive metastatic biliary-tract cancer is discussed for an antibody-drug-conjugate study. The MDT notes that NICE now recommends zanidatamab for eligible IHC3 disease. Which topoisomerase-I antibody-drug conjugate was evaluated in the HERB phase II trial and otherwise requires trial or access-programme availability to be checked?

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Correct answer: B — Trastuzumab deruxtecan, an HER2-directed topoisomerase-I antibody-drug conjugate

HERB evaluated trastuzumab deruxtecan, the HER2-directed topoisomerase-I ADC; NICE TA1153 now makes zanidatamab the routine NHS option for eligible IHC3 disease, so T-DXd access must be checked separately. Trastuzumab emtansine, an HER2-directed microtubule antibody-drug conjugate: T-DM1 has not shown the same biliary-tract activity as trastuzumab deruxtecan. Pertuzumab-trastuzumab, dual HER2 extracellular-domain antibody blockade: dual antibodies are a plausible HER2 strategy but the question asks for the active ADC. Zanidatamab, a biparatopic HER2 antibody with no cytotoxic payload: zanidatamab is a distinct active agent and not the named antibody-drug conjugate. Disitamab vedotin, an HER2-directed microtubule antibody-drug conjugate: this ADC has a different payload and UK access/evidence context.

Reference: HERB phase II trial of trastuzumab deruxtecan in HER2-expressing biliary-tract cancer (Published September 2024): https://pubmed.ncbi.nlm.nih.gov/39102634/; NICE TA1153 zanidatamab for previously treated HER2-positive advanced biliary-tract cancer (Published May 2026): https://www.nice.org.uk/guidance/ta1153/chapter/1-Recommendation