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.

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Patients with previously treated, advanced MSI-H or mismatch repair deficient (dMMR) tumors have limited treatment options. KEYNOTE-158 ( 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.

Read more of Cancer Therapy Advisor’s coverage of ESMO 2021 by visiting the conference page.


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.