|The following article features coverage from the European Society for Medical Oncology (ESMO) Congress 2021. Click here to read more of Cancer Therapy Advisor’s conference coverage.|
Updated results from the phase 2 KEYNOTE-158 study showed a robust and durable overall response rate (ORR) of 48% after pembrolizumab treatment in patients with heavily pretreated advanced endometrial cancer (EC) who had microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors. The results were presented at the European Society for Medical Oncology (ESMO) Congress 2021.
Survival outcomes after treatment with pembrolizumab were encouraging, with 60% estimated to be alive at 4 years, said David O’Malley, MD, of The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center in Columbus.
Patients with previously treated, advanced MSI-H or mismatch repair deficient (dMMR) tumors have limited treatment options. KEYNOTE-158 (ClinicalTrials.gov Identifier: NCT02628067) is a nonrandomized, open-label, phase 2 basket study investigating the antitumor activity and safety of pembrolizumab in multiple cancer types.
In the previous analysis of patients enrolled in cohorts D (advanced endometrial cancer) and K (pan-tumor MSI-H) of the KEYNOTE-158 trial, pembrolizumab showed an ORR of 57% in 49 patients with MSI-H/dMMR advanced EC.
During the long-term follow-up of the study, Dr O’Malley and colleagues evaluated the efficacy of pembrolizumab monotherapy in a larger number of patients with MSI-H/dMMR advanced EC in cohorts D and K.
As of October 5, 2020, 18 of 90 patients (20%) had completed 35 cycles of pembrolizumab, and 52 (58%) had discontinued treatment.
In the efficacy population (79 patients), the median time from the first dose to data cutoff was 42.6 months (range, 6.4-56.1); 41 patients (52%) had 2 lines of prior therapy, and 61% had Eastern Cooperative Oncology Group performance status of 1.
In the efficacy population, pembrolizumab monotherapy yielded an ORR of 48% (95% CI, 36.7-59.6), with complete response in 11 patients (14%), partial response in 27 patients (34%), and stable disease in 14 patients (18%).
The duration of response was more than 3 years in 68% of the patients. The median progression-free survival (PFS) was 13.1 months (95% CI, 4.3-34.4). The 3-year PFS rate was 37%.
The median overall survival (OS) was not reached. The 3-year OS rate was 60%.
Treatment-related adverse events (AEs) were observed in 68 (76%) patients. Of these, 7% of patients discontinued treatment.
Grade 3 to 4 treatment-related AEs occurred in 12% of the patients. Any-grade immune-mediated AEs and infusion reactions occurred in 25 patients (28%). There were no grade 5 AEs.
Overall, the toxicity was manageable and consistent with the toxicity previously observed with pembrolizumab in patients with advanced solid tumors.
In closing remarks, Dr O’Malley stated that “pembrolizumab monotherapy represents a promising treatment option for patients with previously treated MSI-H/dMMR advanced EC.”
Disclosure: This research was supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
O’Malley D, Bariani GM, Cassier PA, et al. Pembrolizumab (pembro) in patients (pts) with microsatellite instability-high (MSI-H) advanced endometrial cancer (EC): Updated results from KEYNOTE-158. Presented at: European Society for Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. Abstract 795MO.