Pembrolizumab shows durable activity in subset of women with endometrial cancer
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Pembrolizumab showed strong and lasting antitumor activity in women with previously treated, advanced microsatellite instability-high or mismatch repair-deficient endometrial cancer, according to a study in Journal of Clinical Oncology.
Results of the open-label, multicohort, phase 2 KEYNOTE-158 study also showed encouraging survival outcomes with the anti-PD-1 antibody, as well as manageable toxicity.
“These findings suggest a long-term benefit to patients. Even the potential for curative intent is now possible in patients with recurrent or metastatic uterine cancer,” David M. O’Malley, MD, professor in the department of obstetrics and gynecology and director of the division of gynecologic oncology at The Ohio State University Comprehensive Cancer Center, said in a press release.
Background and methodology
Although platinum-based chemotherapy regimens, such as carboplatin plus paclitaxel, are standard-of-care first-line therapy for women with advanced or recurrent endometrial cancer, options after treatment failure are limited, O’Malley and colleagues wrote. As many as 31% of women with endometrial cancer have microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) tumors, and pembrolizumab (Keytruda, Merck) has demonstrated activity against these tumors, according to the researchers.
The current analysis included 90 women (median age, 64 years) from two cohorts of KEYNOTE-158 with previously treated, advanced MSI-H/dMMR endometrial cancer.
All women received 200 mg pembrolizumab once every 3 weeks for 35 cycles. Objective response rate served as the primary endpoint; researchers reported duration of response, PFS, OS and safety as secondary endpoints.
By data cutoff, 18 women (20%) had completed all 35 cycles and 52 (58%) had discontinued treatment. Among 79 efficacy-evaluable women who received at least one dose of pembrolizumab and had at least 26 weeks of follow-up, researchers reported a median time from first dose to data cutoff of 42.6 months (range, 6.4-56.1).
Key findings
Nearly half of the women evaluable for efficacy responded to pembrolizumab (ORR = 48%; 95% CI, 37-60), with median duration of response not reached (range, 2.9-49.7+ months).
Additionally, researchers reported median PFS of 13.1 months (95% CI, 4.3-34.4); median OS had not been reached (95% CI, 27.2 months to not reached).
No fatal treatment-related events occurred; immune-mediated adverse events or infusion reactions occurred among 28% of women, and 7% experienced grade 3 to grade 4 immune-mediated adverse events.
Implications
The results demonstrated that commonly used methods of immunohistochemistry (with four mismatch repair proteins) and polymerase chain reaction (using tumor microsatellite loci) can identify women with endometrial cancer who may benefit from pembrolizumab, O’Malley and colleagues wrote.
“By targeting this damaged pathway with this targeted drug, we can reset the cellular mechanisms and allow the immune system to reactivate and attack the cancer cells,” O’Malley said.
References:
Immunotherapy drug shows promise in advanced endometrial cancer. https://cancer.osu.edu/news/immunotherapy-drug-shows-promise-in-advanced-endometrial-cancer. Published Jan. 6, 2022. Accessed Jan. 14, 2022.
O’Malley DM, et al. J Clin Oncol. 2021;doi:10.1200/JCO.21.01874.
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