In an analysis reported in the Journal of Clinical Oncology, Vicky Makker, MD, and colleagues provided updated findings from the phase Ib/II Study 111/KEYNOTE-146 trial of lenvatinib and pembrolizumab in previously treated patients with advanced endometrial carcinoma.
The study supported the September 2019 accelerated approval of the combination in patients with disease that is not mismatch repair–proficient (pMMR) or not microsatellite instability–high (MSI-H), a subgroup that comprised 87% of the study population. Full approval of the combination in this setting was granted in July 2021 on the basis of the phase III Study 309/KEYNOTE-775 trial.
Vicky Makker, MD
In the study, 108 patients who had received no more than two prior systemic therapies received lenvatinib at 20 mg daily plus pembrolizumab at 200 mg every 3 weeks. Among patients with known status, 94 had non–MSI-H/pMMR disease and 11 had MSI-H/mismatch repair–deficient disease. In the primary analysis, investigator-assessed objective response rate on immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) criteria was 38.9% (95% confidence interval [CI] = 29.7%–48.7%); median duration of response was 21.2 months (95% CI = 7.6 months to not estimable); median progression-free survival on irRECIST was 7.4 months (95% CI = 5.3–8.7 months); median overall survival was 16.7 months (95% CI = 15.0 months to not estimable).
The current analysis among the 108 patients in the primary analysis occurred after a median follow-up of 34.7 months (95% CI = 30.9–41.2 months).
Among all patients, the objective response rate on irRECIST was 39.8% (95% CI = 30.5%–49.7%) and median duration of response was 22.9 months (95% CI = 10.2 months to not estimable). Median progression-free survival was 7.4 months (95% CI = 5.2–8.7 months) and median overall survival was 17.7 months (95% CI = 15.5–25.8 months).
Among the 94 patients with non–MSI-H/pMMR disease, the objective response rate on irRECIST was 38.3% (95% CI = 28.5%–48.9%) and median response duration was 23.0 months (95% CI = 8.5 months to not estimable), with some responses ongoing at 4 years. Median progression-free survival was 7.4 months (95% CI = 4.4–7.6 months) and median overall survival was 17.2 months (95% CI = 15.0–25.8 months).
Treatment-related grade ≤ 3 adverse events occurred in 87.0% of patients, and treatment-related grade ≥4 events occurred in 9.3%. The most common grade ≥ 3 treatment-related adverse events were hypertension (in 33.3% of patients), elevated lipase (9.3%), fatigue (8.3%), and diarrhea (7.4%). Treatment-related serious adverse events occurred in 32.4% of patients, most commonly hypertension (6.5%). Two treatment-related deaths had occurred at time of primary analysis; no further treatment-related deaths occurred over longer-term follow-up.
The investigators concluded, “The results demonstrate extended efficacy and tolerability of lenvatinib plus pembrolizumab in this cohort of patients with previously treated advanced endometrial carcinoma.”
Dr. Makker, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Eisai Inc, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co Inc. For full disclosures of the study authors, visit ascopubs.org.