Skip to content

Pembrolizumab in MSI-high advanced colorectal cancer

One-paragraph summary

KEYNOTE-177 randomized 307 untreated MSI-high/dMMR metastatic patients to pembrolizumab or investigator-choice chemotherapy. Median progression-free survival was 16.5 versus 8.2 months (HR 0.60, 95% CI 0.45–0.80); grade ≥3 treatment-related adverse events occurred in 22% versus 66% (PMID 33264544).

Key findings

  • First-line checkpoint blockade more than doubled median PFS.
  • Toxicity was materially lower than cytotoxic/biologic control.
  • Responses were more durable, but early progression occurred in a subset.
  • MMR/MSI became an urgent pretreatment result rather than a later-line test.

Limitations

  • Open-label design and extensive crossover complicated OS.
  • MSI/MMR assay heterogeneity and occasional misclassification matter.
  • Results do not apply to MMR-proficient disease.
  • It did not compare single-agent with dual-checkpoint therapy.

Why it matters

The trial moved pembrolizumab to first line and made universal, timely MMR/MSI testing an operational treatment requirement.

Cited by wiki pages

  • Overview
  • Metastatic systemic therapy
  • Precision oncology