EU approves Keytruda for metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer.- Merck Inc

Merck Inc announced that the European Commission has approved Keytruda (pembrolizumab), 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 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 (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 at least 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.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.