KEYNOTE-755 Confirms Broad Efficacy of Lenvatinib Plus Pembrolizumab in Advanced Endometrial Cancer

The phase 3 KEYNOTE-755 trial established lenvatinib (Lenvima; Eisai) plus pembrolizumab (Keytruda; Merck) as a key treatment option for patients with previously treated advanced or metastatic endometrial cancer. The combination significantly improved progression-free and overall survival compared with standard chemotherapy, with consistent benefit across both mismatch repair (MMR)-proficient and -deficient disease.

In an interview with Pharmacy Times, Vicky Makker, MD, discussed the pivotal findings, the implications for real-world practice, and how the regimen’s activity spans molecular subtypes of endometrial cancer.

Q: Could you summarize the key efficacy outcomes from the KEYNOTE-775 trial, particularly regarding overall survival and progression-free survival compared with the treatment of physician’s choice?
Vicky Makker, MD: KEYNOTE-775 was a randomized global phase 3 clinical trial in patients with advanced or previously treated endometrial cancers. All patients had prior platinum-based chemotherapy and were stratified by mismatch repair (MMR) status.

Patients were randomized 1:1 to receive the VEGF TKI lenvatinib plus the PD-1 inhibitor pembrolizumab versus treatment of physician’s choice, which included either doxorubicin or weekly paclitaxel. The primary endpoints were progression-free survival, assessed by blinded review, and overall survival.

When the primary results were presented, we found significant improvement in objective response rate, progression-free survival, and overall survival with lenvatinib plus pembrolizumab compared with treatment of physician’s choice. This benefit was observed across the MMR-proficient, MMR-deficient, and overall populations. These results led to the approval of lenvatinib plus pembrolizumab as a standard-of-care option for patients with previously treated advanced or metastatic endometrial cancer.

Q: What do the results tell us about the activity of lenvatinib plus pembrolizumab across patient subgroups, especially those with mismatch repair–proficient versus deficient disease?
Makker: Lenvatinib plus pembrolizumab was previously evaluated in a basket trial across many solid tumors, including both MMR-proficient and MMR-deficient endometrial cancers. In that trial, we saw compelling activity of this regimen regardless of MMR status.

KEYNOTE-775 confirmed those findings, showing strong efficacy not only in MMR-proficient endometrial cancers—which comprise the majority of recurrent disease—but also encouraging results in the MMR-deficient population. This regimen therefore appears to benefit endometrial cancers regardless of molecular phenotype.