MSI-H CRC Immunotherapy — RACP Adult Medicine MCQ

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ModerateMedical OncologyMSI-H CRC ImmunotherapyRACP Adult Medicine

A 55-year-old woman with metastatic colorectal cancer undergoes tumour profiling. Her tumour is microsatellite instability-high (MSI-H) / deficient mismatch repair (dMMR). What is the preferred first-line systemic therapy?

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Correct answer: B — Pembrolizumab monotherapy

For metastatic CRC that is MSI-H/dMMR (~15% of CRC), first-line pembrolizumab monotherapy is now the standard of care based on the KEYNOTE-177 trial, which showed superior PFS compared to chemotherapy. Complete response rates are significantly higher with immunotherapy in MSI-H CRC. This is a paradigm shift – chemotherapy is no longer first-line for MSI-H mCRC. The MSI-H/dMMR phenotype should be tested in ALL newly diagnosed metastatic CRC patients. It may also indicate Lynch syndrome requiring germline testing.

Reference: Cancer Council Australia – 2022 – CRC OCP; PBS – 2025 – Pembrolizumab mCRC Listing