Long-term follow-up from the phase 2 KEYNOTE-158 trial showed enduring anti-tumor activity when pembrolizumab was used to treat patients with microsatellite instability–high/mismatch repair deficient advanced endometrial cancer.
Sustained anti-tumor activity was observed when patients with microsatellite instability–high (MSI-H)/mismatch repair deficient (dMMR) advanced endometrial cancer, who experienced progressive disease following systemic therapy and who are ineligible for curative surgery or radiation, were treatment with pembrolizumab (Keytruda), according to long-term follow-up results from the phase 2 KEYNOTE-158 trial (NCT02628067).
Treatment yielded an objective response rate (ORR) of 50%, and an estimated duration of response (DOR) rate of 4 years or more of 66%. Additionally, 59% of patients were estimated to be alive after 4 years. The poster was presented at the 2022 European Society for Medical Oncology by David O’Malley, MD, director of the Division of Gynecologic Oncology at the Ohio State University Comprehensive Cancer Center.
The presentation focused on patients enrolled in cohorts D, those with endometrial cancer regardless of MSI-H/dMMR status, and cohort K, any MSI-H/dMMR solid tumor except for colorectal, of the KEYNOTE-158 trial. A total of 94 patients were included in the study who were treated with 200 mg of pembrolizumab intravenously every 3 weeks for 35 cycles or until disease progression, toxicity, investigator choice, or patient withdrawal.
The primary end point was ORR, with secondary end points including DOR, progression-free survival (PFS), overall survival (OS), and safety.
Patients were eligible to enroll if they had MSI-H/dMMR advanced endometrial cancer, progression or intolerance to 1 or more lines of therapy, measurable disease, an ECOG performance status of 0 or 1, and an available tumor sample for biomarker assessment.
The median time from the first dose of treatment to data cutoff was 54.5 months. At data cutoff, 23% of patients had completed treatment, 71% had discontinued, and 5% remained on treatment.
The median patient age was 64 years, and 55% of patients had an ECOG performance status of 1. The majority of patients had M1 disease (96%). Moreover, 52% of patients had 1 prior line of therapy, 22% had 2, 16% had 3, and 10% had 4 or more. Prior adjuvant or neoadjuvant therapy was given to 27% of patients, 67% had prior radiation, and 86% had prior surgery.
The ORR was 40% for those who received prior neoadjuvant or adjuvant therapy (n = 10), 59% for those with 1 prior line of therapy (n = 39), and 44% in those with more than 1 prior lines of therapy (n = 45). Overall, 16% of patients had a complete response, 34% had a partial response, 18% had stable disease, and 28% had progressive disease.
The median DOR was 63.2 months (95% CI, 2.9-63.2) among the 47 responders. At 1 year, the DOR rate was 87%, 71% at 2 years, 66% at 3 years, and 66% at 4 years. The median PFS, was 13.1 months (95% CI, 4.3-25.7). At 1 year the PFS rate was 50%, 41% at 2 years, and 37% at 3 and 4 years, respectively. The median OS was 64.5 months (95% CI, 29.5-not reached). At 1 year, OS rate was 70%, 64% at 2 years, and 59% at 3 and 4 years.
Treatment-related adverse effects (TRAEs) of any grade occurred in 76% of patients, 14% of which were grade 3/4. The most common any grade TRAEs were pruritus (26%), fatigue (20%), diarrhea (17%), and arthralgia (16%). In total, 8 patients discontinued treatment due to AEs. Immune-mediated AEs of any grade occurred in 30% of patients, 9% of whom had grade 3/4 toxicities. The most common any grade AEs were hypothyroidism (16%), hyperthyroidism (7%), colitis (4%), and infusion reactions (3%). Grade 3/4 toxicities included infusion reactions (3%), colitis (2%), type 1 diabetes mellitus (1%), hepatitis (1%), and myositis (1%).
O’Malley DO, Bariani GM, Cassier PA, et al. Pembrolizumab for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) advanced endometrial cancer: long-term follow-up results from KEYNOTE-158. Ann Oncol. 2022;33(suppl 7):546P. doi:10.1016/annonc/annonc1054