Endometrial cancer begins in the lining of the uterus and is one of the few tumor types whose death rate is still rising. For decades the opening move against advanced disease has been a platinum-based chemotherapy pairing, with immunotherapy added or reserved for later. Merck set out to test whether its PD-1 blocker could replace that regimen entirely for patients whose tumors carry mismatch repair defects, a flaw that tends to make cancers responsive to immune checkpoint drugs. Keytruda alone cut the risk of progression or death by 43% compared with chemotherapy in that group, Merck said in a release on Monday.
The direction of the result was known; the size was not. In July Merck said the trial had met its progression-free survival endpoint, making Keytruda the first PD-1 inhibitor to beat a platinum doublet as monotherapy in a Phase 3 study in this setting, while a trend toward longer overall survival was not yet mature and would be assessed in a later analysis, the company said at the time. Survival data will shape how regulators and treatment guidelines weigh the findings.
The competitive context is crowded. ApexOnco framed the result as a direct challenge to AstraZeneca and GSK in the front-line dMMR setting, while cautioning that pairing immunotherapy with chemotherapy will still serve some patients better, the clinical trials publication wrote.
Keytruda is no stranger to this disease. It is approved as a single agent for microsatellite-unstable or mismatch repair-deficient solid tumors, including endometrial carcinoma, in patients who have progressed after earlier therapy. Pushing the drug into first-line use matters for a company that assumes U.S. exclusivity for Keytruda ends in 2028, its filings and earnings calls show.