Work

Lenvatinib starting doses below 20 mg versus 20 mg with pembrolizumab in advanced or recurrent endometrial cancer: a systematic review and meta-analysis of comparative observational evidence

Year: 2026

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: Background: Lenvatinib plus pembrolizumab is an established treatment for patients with previously treated advanced or recurrent endometrial cancer. In routine practice, clinicians may select a lenvatinib starting dose below 20 mg for patients expected to have limited tolerance, but the comparative effectiveness and tolerability of that strategy remain uncertain. Methods: We searched PubMed/MEDLINE, Web of Science Core Collection, and Cochrane CENTRAL from inception to 11 July 2026, with source-specific updates completed on 13-14 July 2026. Comparative observational studies of adults receiving lenvatinib plus pembrolizumab were eligible. The primary estimand compared starting doses below 20 mg with 20 mg; a 10-mg threshold contrast and first-8-week relative dose intensity were kept separate. Binary outcomes were summarized as risk ratios (RRs) and time-to-event outcomes as hazard ratios (HRs). Risk of bias was assessed with ROBINS-I, missing-evidence bias with ROB-ME, and certainty with GRADE. Results: Ten studies representing 10 independent cohorts and 1,000 patients were included. Five cohorts (703 patients in total) informed the primary starting-dose comparison, with outcome-specific analysis denominators. For starting doses below 20 mg versus 20 mg, the pooled RR was 0.97 for objective response (95% confidence interval [CI], 0.70-1.34; I²=11.9%) and 0.96 for disease control (95% CI, 0.83-1.11; I²=0%). The RR for subsequent lenvatinib dose reduction was 0.66 (95% CI, 0.34-1.27; I²=27.4%). Estimates for interruption, permanent discontinuation, grade 3 or higher adverse events, and progression-free survival were imprecise; hospitalization and treatment persistence were not poolable. Every evaluated result had serious overall risk of bias, and certainty was very low for all pooled comparisons. Conclusion: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261458417.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1965694