The European Commission has approved Keytruda as a monotherapy for the first-line treatment of adult patients with metastatic microsatellite instability-high or mismatch repair deficient colorectal cancer.
Keytruda is sponsored by Merck.
This approval is based on results from the pivotal phase III KEYNOTE-177 trial, in which Keytruda monotherapy significantly reduced the risk of disease progression or death by 40% (HR=0.60 [95% CI, 0.45-0.80]; p=0.0002) compared with chemotherapy (investigator’s choice: mFOLFOX6 [oxaliplatin, leucovorin and fluorouracil (FU)] with or without bevacizumab or cetuximab; or FOLFIRI [irinotecan, leucovorin and FU] with or without bevacizumab or cetuximab).
In the trial, treatment with Keytruda also more than doubled median progression-free survival compared with chemotherapy (16.5 months [95% CI, 5.4-32.4] versus 8.2 months [95% CI, 6.1-10.2]).
This approval marks the first gastrointestinal indication for Keytruda in Europe and makes Keytruda the first anti-PD-1/L1 therapy approved in Europe for these patients.
This approval allows marketing of Keytruda monotherapy in all 27 European Union member states plus Iceland, Lichtenstein, Norway and Northern Ireland. Following Brexit, in line with the reliance route, this approval is also valid in Great Britain.
The approval was based on data from KEYNOTE-177, a multi-center, randomized, open-label, active-controlled trial that enrolled 307 patients with previously untreated metastatic MSI-H or dMMR colorectal cancer.
Microsatellite instability or mismatch repair tumor status was determined locally using polymerase chain reaction or immunohistochemistry, respectively. Patients with autoimmune disease or a medical condition that required immunosuppression were ineligible.
Patients were randomized 1:1 to receive Keytruda (200 mg intravenously) every three weeks or investigator’s choice of the following chemotherapy regimens given intravenously every two weeks:
mFOLFOX6 (oxaliplatin, leucovorin and FU) or mFOLFOX6 in combination with either bevacizumab or cetuximab: oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 (or levoleucovorin 200 mg/m2), and FU 400 mg/m2 bolus on Day 1, then FU 2,400 mg/m2 over 46-48 hours; plus bevacizumab 5 mg/kg on Day 1 or cetuximab 400 mg/m2 on first infusion, then 250 mg/m2 weekly
FOLFIRI (irinotecan, leucovorin, and FU) or FOLFIRI in combination with either bevacizumab or cetuximab: irinotecan 180 mg/m2, leucovorin 400 mg/m2 (or levoleucovorin 200 mg/m2), and FU 400 mg/m2 bolus on Day 1, then FU 2,400 mg/m2 over 46-48 hours; plus bevacizumab 5 mg/kg on Day 1 or cetuximab 400 mg/m2 on first infusion, then 250 mg/m2 weekly
Treatment with Keytruda or chemotherapy continued until Response Evaluation Criteria in Solid Tumors (RECIST) v1.1-defined progression of disease as determined by the investigator or unacceptable toxicity.
Patients treated with Keytruda without disease progression could be treated for up to 24 months.