ASCO 2020 – Pembrolizumab shows unprecedented promise in metastatic CRC subtype


  • Jim Kling
  • Oncology Conference reports
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Takeaway

  • Treatment with pembrolizumab improved progression-free survival (PFS) compared with chemotherapy in microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC).

Why this matters

  • The approximately doubled improvement in PFS is greater than any seen in previous mCRC therapies.
  • Approximately 5% of mCRC patients are MSI-H/dMMR.

Study design

  • 307 patients with MSI-H/dMMR mCRC who had good performance status were randomly assigned to up to 35 cycles of pembrolizumab (200 mg every 3 weeks) or investigators' choice of chemotherapy, including modified FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) with or without bevacizumab or cetuximab or FOLFIRI (leucovorin, fluorouracil, irinotecan) with or without either bevacizumab or cetuximab (KENOTE-177).
  • Funding: MSD.

Key results

  • The pembrolizumab group vs the chemotherapy group had a longer median PFS (16.5 months vs 8.2 months; HR, 0.60; P=.0002) and higher 12-month (55% vs 37%) and 24-month (48% vs 19%) PFS rates.
  • The pembrolizumab group had a higher overall response rate (43.8%; 11.1% complete and 32.7% partial) than the chemotherapy group (33.1%; 3.9% complete and 29.2% partial).
  • The rate of stable disease was lower in the pembrolizumab group (20.9% vs 42.2%).
  • 29.4% of the pembrolizumab group had progressive disease compared with 12.3% of the chemotherapy group.
  • At 2 years, the ongoing response rate was 83% in the pembrolizumab group vs 35% in the chemotherapy group.
  • Adverse events in pembrolizumab vs chemotherapy group:
    • Grade ≥3 treatment-related adverse events: 22% vs 66%.
    • Immune-mediated adverse events and infusion reactions: 31% vs 13%.

Limitations

  • Standard of care active comparator arm included 6 different treatment options.

Expert Commentary

  • “I think this is setting a new standard of care,” said Michael J. Overman, MD, of the University of Texas MD Anderson Cancer Center in Houston, who was an invited discussant for the presentation of the research.
  • “The only area where I think the question on pembrolizumab is still open would be in the group of patients where we're saying ‘I care about the near future’ — this patient has so many symptoms and so much disease burden that I care what happens in the short term,” said Dr Overman. In this group of patients, he said it might be better to combine chemotherapy or pembrolizumab with another immunotherapy, such as ipilimumab.