European Commission Approves KEYTRUDA? (pembrolizumab) as First-Line Treatment in Adult Patients With Metastatic Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Co
KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced today that the European Commission has approved KEYTRUDA, Merck?s anti-PD-1 therapy, as a monotherapy for the first-line treatment of adult patients with metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. This approval is based on results from the pivotal Phase 3 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 (PFS) compared with chemotherapy (16.5 months [95% CI, 5.4-32.4] versus 8.2 months [95% CI, 6.1-10.2]).?There was a lower incidence of Grade =3 treatment-related adverse events (TRAEs) with KEYTRUDA compared with chemotherapy (22% versus 66%), and no new toxicities were observed.?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.
?Before the KEYNOTE-177 trial, conventional chemotherapy with targeted therapy was the standard of care for patients with metastatic colorectal cancer who have tumors that are MSI-H/dMMR,? said Dr. Thierry Andre, professor of medical oncology at Sorbonne University and head of the medical oncology department at St. Antoine Hospital, Assistance Publique H?pitaux de Paris. ?With this approval, patients with metastatic colorectal cancer that is MSI-H or dMMR status will gain a monotherapy treatment option that has shown superior progression-free survival compared to standard of care chemotherapy.?
?This decision by the European Commission, which was based on the important findings from KEYNOTE-177, exemplifies our commitment to using biomarkers such as MSI/MMR to help identify patients who are most likely to respond to KEYTRUDA,? said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. ?Our efforts in biomarker-driven research across tumor types ? including colorectal cancer, the most common type of gastrointestinal cancer ? will continue to help us bring new options to patients across the globe.?
This approval allows marketing of KEYTRUDA monotherapy in all 27 European Union (EU) 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.
Data Supporting the European Approval
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 (MSI) or mismatch repair (MMR) 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
- solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
- colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.