Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer

Abstract

Purpose: Patients with advanced endometrial carcinoma have limited treatment options. We report final primary efficacy analysis results for a patient cohort with advanced endometrial carcinoma receiving lenvatinib plus pembrolizumab in an ongoing phase Ib/II study of selected solid tumors.

Methods: Patients took lenvatinib 20 mg once daily orally plus pembrolizumab 200 mg intravenously once every 3 weeks, in 3-week cycles. The primary end point was objective response rate (ORR) at 24 weeks (ORR_Wk24); secondary efficacy end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Tumor assessments were evaluated by investigators per immune-related RECIST.

Results: At data cutoff, 108 patients with previously treated endometrial carcinoma were enrolled, with a median follow-up of 18.7 months. The ORR_Wk24 was 38.0% (95% CI, 28.8% to 47.8%). Among subgroups, the ORR_Wk24 (95% CI) was 63.6% (30.8% to 89.1%) in patients with microsatellite instability (MSI)-high tumors (n = 11) and 36.2% (26.5% to 46.7%) in patients with microsatellite-stable tumors (n = 94). For previously treated patients, regardless of tumor MSI status, the median DOR was 21.2 months (95% CI, 7.6 months to not estimable), median PFS was 7.4 months (95% CI, 5.3 to 8.7 months), and median OS was 16.7 months (15.0 months to not estimable). Grade 3 or 4 treatment-related adverse events occurred in 83/124 (66.9%) patients.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT02501096.

FIG 1.

Percentage change in sum of diameters of target lesions from baseline to post-baseline nadir by microsatellite instability/mismatch-repair (MSI/MMR) status (by investigator assessment; using immune-related RECIST). dMMR, MMR deficient; m, the number of previously treated patients with both baseline and at least 1 postbaseline target lesion assessment; MSI-H, MSI-high; pMMR, MMR proficient; PD-1, programmed death receptor-1; PD-L1, programmed death-ligand 1.

FIG 2.

Kaplan-Meier plot of (A) duration of response, (B) progression-free survival, and (C) overall survival assessed by the investigator per immune-related RECIST (for A and B groups only; not appropriate for C) in patients with endometrial cancer previously treated with systemic therapies. dMMR, mismatch-repair deficient; EC 2L+, endometrial cancer second-line (or greater) treatment MSI-H, microsatellite instability high; MSS, microsatellite stable; NE, not estimable; pMMR, mismatch-repair proficient.

FIG 3.

Percentage change in sum of diameters of target lesions from baseline to post-baseline nadir by histologic subtype (by investigator assessment; using immune-related RECIST). m, the number of previously treated patients with both baseline and at least 1 postbaseline target lesion assessment.