Use of Inhibitor Combination Based on MSI Status in Endometrial Cancer

Bhavana Pothuri, MD, professor in the Department of Obstetrics and Gynecology and Department of Medicine at NYU Grossman School of Medicine, and director of Gynecologic Oncology Clinical Trials at NYU Langone Health’s Perlmutter Cancer Center, discusses the results of the KEYNOTE-775 trial (NCT03517449) in patients with advanced endometrial cancer in relation to microsatellite instability (MSI) status.

According to Pothuri, the randomized phase 3 KEYNOTE-775 trial of pembrolizumab (Keytruda) and lenvatinib (Lenvima) showed superior progression-free survival (PFS) and overall survival (OS) versus doxorubicin or paclitaxel in patients who had been previously treated with platinum-based chemotherapy. However, the combination of pembrolizumab and lenvatinib was approved for patients without MSI-high (MSI-H) status or a mismatch repair deficiency (dMMR) based on the study results.

Therefore, Pothuri says that it is important to test for MSI status using polymerase chain reaction or next-generation sequencing testing to identify patients who are microsatellite stable (MSS) and can receive a checkpoint inhibitor combination as second-line therapy.

TRANSCRIPTION:

0:08 | It's really important to know which patients are MSI-H, or which patients are MSS, and for MSS tumors, they are candidates for combination treatment with lenvatinib and pembrolizumab. And this is based on the data that were presented and published from KEYNOTE-775, which was a randomized phase 3 trial. The trial met its end points of both PFS, as well as OS. So really, these findings have led to the full approval of this combination in the treatment of recurrent endometrial cancer that's MSS. And that's why I say at minimum, it's really important to at least sort out those 2 subgroups: the MSS and MSI-H, or dMMR.