Pembrolizumab Shows Long-Term Responses in MSI-H/dMMR Endometrial Cancer

David O’Malley, MD, a professor in the department of obstetrics and gynecology at The Ohio State University College of Medicine and the director of the division of gynecologic oncology at the OSUCCC–James, discusses updated results from the KEYNOTE-158 trial (NCT02628067) of pembrolizumab (Keytruda) in patients with advanced endometrial cancer.

The open-label, multicohort, phase 2 KEYNOTE-158 study retrospectively analyzed patients enrolled in the trial who had microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) advanced endometrial cancer. Data from this analysis presented at the European Society for Medical Oncology 2022 Congress showed that this subset of patients had an objective response rate (ORR) of 50%. For those who had 1 prior line of therapy, ORR was 59% versus 44% for those who received multiple prior lines.

Notably, the rate of durable response at 4 years was 66%, suggesting pembrolizumab is effective as long-term treatment that potentially cures some patients, O’Malley says. In terms of overall survival (OS), the 4-year OS rate was 59% in all patients, including those who did not respond, and it was 66% in responders. This shows that patients with recurrent MSI-H/dMMR endometrial cancer can have long-term survival with pembrolizumab.

TRANSCRIPTION:

0:08 | It was fairly consistent between 1 prior therapy and more than 1 prior to therapy: [an ORR of] 59% versus 44%. But a really important aspect of this is that of the 50% ORR, you had a two-thirds chance of extending that beyond 4 years, potentially curing two-thirds of women with recurrent endometrial cancer. And when we look at the OS of the entire cohort, at 4 years, 59% of those patients were alive—the entire cohort, not just those who responded—so if you responded, the chance that [OS] extended beyond 4 years or more was 66%. We're really talking about potentially curing women with recurrent [endometrial] cancer who have dMMR deficient or MSI-H.