First-line pembrolizumab shows promise in microsatellite-instability-high CRC

  • André T & al.
  • N Engl J Med
  • 3 Dec 2020

  • curated by Jim Kling
  • Univadis Clinical Summaries
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Takeaway

  • In a phase 3 trial, pembrolizumab led to better PFS than chemotherapy in first-line treatment of microsatellite-instability-high mismatch-repair deficiency advanced colorectal cancer (CRC).

Why this matters

  • Pembrolizumab is FDA approved in this group after progression following chemotherapy.

Study design

  • Interim analysis of a phase 3, open-label trial (KEYNOTE-177; n=307).
  • Patients were randomly assigned to 200 mg pembrolizumab every 3 weeks or chemotherapy (5-fluorouracil-based therapy with or without bevacizumab or cetuximab) every 2 weeks.
  • Funding: Merck Sharp and Dohme; Stand Up to Cancer.

Key results

  • Median PFS was higher in the pembrolizumab group:
    • 16.5 vs 8.2 months. 
    • HR, 0.60 (P=.0002).
  • More patients were free of progression in the pembrolizumab group at 12 months (55.3% vs 37.3%) and 24 months (48.3% vs 18.6%).
  • After 24 months of follow-up, the mean period of PFS was higher in the pembrolizumab group (13.7 vs 10.8 months).
  • Among patients with a complete or partial response, at 24 months 83% in the pembrolizumab were ongoing vs 35% in the chemotherapy group.
  • Adverse events grade ≥3 were less common in the pembrolizumab group (56% vs 78%).

Limitations

  • Open label.