Five-Year KEYNOTE-775 Data Confirm Durable Benefit With Lenvatinib Combo

Susana M. Campos, MD, MPH, clinical director of the Division of Gynecologic Oncology and director of Educational Initiatives at Dana-Farber Cancer Institute, and assistant professor of medicine at Harvard Medical School, reviewed 5-year follow-up data from the phase 3 Study 309/KEYNOTE-775 trial (NCT03517449), which evaluated lenvatinib (Lenvima) plus pembrolizumab (Keytruda) against chemotherapy in previously treated advanced endometrial cancer. Among 827 patients followed for a median of 68 months, the combination showed a durable survival benefit in the mismatch repair-deficient (dMMR) cohort.

As part of a Satellite Sessions post-program conversation, Campos weighed whether these data are strong enough to make the combination a default second-line choice, balancing the survival benefit against treatment-related adverse events.

Transcript:

CancerNetwork: In light of the 5-year data from KEYNOTE-775, is the efficacy robust enough to make lenvatinib plus pembrolizumab your default second-line choice for dMMR disease, even after a frontline IO/chemotherapy regimen?

Campos: It depends on what’s available to the patient. When you look at the KEYNOTE-775 data, which were updated in February 2026, there is a durable long-term benefit of lenvatinib and pembrolizumab, and it was a sizable study: 827 patients, with a median follow-up of 68 months. When they looked at 5-year overall survival, it was as high as 37% in the dMMR cohort, and 5-year progression-free survival was as high as 26%. The caveat is that treatment-related adverse events did lead to some discontinuation, which can be as high as 32%. I don’t know that this makes it an automatic default, especially in patients who’ve been previously treated with IO, but it’s certainly a contender by all means. We have to weigh the options available to patients when they recur. It’s important to remember that KEYNOTE-775 is a very valuable study, but it did not study patients who had prior IO. We’re in a little bit of uncharted waters. However, it’s certainly a contender in the management of patients. When you’re seeing patients on a clinical level, you look to other elements: Is there a HER2/neu expression? Are there clinical trials the patient can enroll on? Is the patient a candidate for hormonal therapy if we’re looking at endometrial cancer? What novel ADCs would you like to treat the patient with before they’ve accrued too many prior lines of therapy and are no longer eligible for a trial? It’s an individualized basis, tailored to the individual at hand.

Reference

Makker V, Colombo N, Casado A, et al. Lenvatinib plus pembrolizumab in previously treated advanced endometrial cancer: 5-year outcomes from the randomized, phase 3 Study 309/KEYNOTE-775. J Immunother Cancer. 2026;14(2):e013713. doi:10.1136/jitc-2025-013713