As reported in the Journal of Clinical Oncology by Vicky Makker, MD, and colleagues, findings from a phase Ib/II trial indicate that the combination of lenvatinib and pembrolizumab is active in patients with previously treated advanced endometrial carcinoma.

Vicky Makker, MD

Study Details

The report is the primary efficacy analysis of 108 previously treated patients in a cohort of 124 patients with advanced endometrial carcinoma. These patients are enrolled in an ongoing phase Ib/II study of those with select solid tumors. Patients received lenvatinib at 20 mg once daily plus pembrolizumab at 200 mg every 3 weeks in 3-week cycles. Prior treatment included platinum/taxane therapy in 98% of patients. The primary endpoint was objective response rate at 24 weeks.

Responses

Median follow-up was 18.7 months. Objective response at week 24 was achieved in 41 (38.0%) of 108 previously treated patients. Objective response at week 24 was observed in 34 (36.2%) of 94 patients with microsatellite-stable (MSS)/mismatch repair–proficient (pMMR) disease and in 7 (63.6%) of 11 with microsatellite instability–high (MSI-H)/mismatch repair–deficient (dMMR) tumors.

Overall, objective response was observed in 42 (38.9%) of the 108 previously treated patients, including complete response in 8 (7.4%). Response rates were 35.8% among 53 patients with programmed cell death ligand 1 (PD-L1)-positive tumors, 39.5% among 43 with PD-L1–negative tumors, 37.2% among those with MSS/pMMR tumors, and 63.6% among those with MSI-H/dMMR tumors. Median duration of response was 21.2 months; median progression-free survival was 7.4 months; and median overall survival was 16.7 months. 

Adverse Events

Among the 124 patients receiving treatment (including the 16 who had not received previous treatment), grade 3 or 4 treatment-related adverse events occurred in 66.9%, with the most common being hypertension (31.5%) and fatigue (7.3%). Adverse events led to discontinuation of one or both study drugs in 22 patients (17.7%). Prespecified adverse events of any grade associated with pembrolizumab occurred in 57.3% of patients, with the most common being hypothyroidism (47.6%).

The investigators concluded, “Lenvatinib plus pembrolizumab showed promising antitumor activity in patients with advanced endometrial carcinoma who have experienced disease progression after prior systemic therapy, regardless of tumor MSI status. The combination therapy had a manageable toxicity profile.”

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 Corp, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit ascopubs.org.