Efficacy and safety of pembrolizumab-lenvatinib in metastatic endometrial cancer: results from the French multicenter early access program.
Abstract
Background
Pembrolizumab-lenvatinib (P/L) is a standard option for patients with advanced or metastatic endometrial cancer (a/m EC) progressing after platinum-based chemotherapy, based on the KEYNOTE-775 trial. However, concerns remain regarding its real-world applicability, particularly in older, frailer patients and in aggressive histological subtypes underrepresented or excluded from pivotal trials. This study aimed to evaluate the effectiveness and tolerability of P/L in routine practice through the French early access program (EAP). PATIENTS AND
Methods
We conducted a multicenter retrospective analysis of patients treated within the national EAP between March 2022 and December 2023. Eligible patients had histologically confirmed a/m EC progressing after platinum. Pembrolizumab was administered at 200 mg every 3 weeks, and lenvatinib was initiated at up to 20 mg daily. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods, and prognostic factors explored with Cox regression.
Results
A total of 351 patients from 25 centers were included [median age 73 years; 21.5% Eastern Cooperative Oncology Group (ECOG) ≥2]. Carcinosarcomas represented 8.9% of cases. Median PFS was 6.0 months [95% confidence interval (CI) 5.7-8.3], and median OS was 21 months (95% CI 18.6-22.9). Mismatch repair-deficient status was strongly associated with prolonged PFS (16 versus 6 months, P < 0.001). Objective response rate at 6 months was 41%, with a clinical benefit rate of 68%. Independent adverse prognostic factors for PFS included ECOG >1, multiple metastatic sites, microsatellite stable status, and carcinosarcoma subtype. Reduced starting lenvatinib dose (37.2% of patients) did not adversely impact PFS. Permanent discontinuation of lenvatinib because of toxicity was observed in 96 patients (27.6%).
Conclusions
P/L demonstrates meaningful activity in a broad real-world population, including older patients with more aggressive disease features and those starting at reduced lenvatinib doses. These findings support the sustained benefit of this combination beyond clinical trial settings, provided that lenvatinib is carefully monitored and doses are personalized.