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
- 1Dongzhimen Hospital, Beijing University of Chinese Medicine
- 2School of Life Science, Beijing University of Chinese Medicine
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: Comparative observational evidence does not establish that starting lenvatinib below 20 mg preserves antitumor effectiveness or improves tolerability relative to a 20 mg starting dose. Prospective, confounder-aware comparative studies are needed before a reduced starting-dose strategy can be recommended broadly.
Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420261458417.
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BibTeX
@article{wu2026lenvatinib,
title = {{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}},
author = {Yu Wu and Juncheng Wei and Chuyue Chang and Mengfei Li and Runbing Xu and Shi Dong and Miao Jiang},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1965694},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1965694/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Yu Wu
AU - Juncheng Wei
AU - Chuyue Chang
AU - Mengfei Li
AU - Runbing Xu
AU - Shi Dong
AU - Miao Jiang
PY - 2026
DA - 2026/10/16
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1965694
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1965694/full
AB - 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: Comparative observational evidence does not establish that starting lenvatinib below 20 mg preserves antitumor effectiveness or improves tolerability relative to a 20 mg starting dose. Prospective, confounder-aware comparative studies are needed before a reduced starting-dose strategy can be recommended broadly. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420261458417.
SN - 2234-943X
ER -