Efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer: a systematic review and meta-analysis

Front Immunol. 2024 Aug 9:15:1404669. doi: 10.3389/fimmu.2024.1404669. eCollection 2024.

Abstract

Background: Various trials have demonstrated the clinical benefits of lenvatinib plus pembrolizumab in patients with advanced or recurrent endometrial cancer, regardless of mismatch repair (MMR) status or histologic subtype. The majority of the previously published trials had small sample sizes. Here, we aimed to assess the reported efficacy and safety profile of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer.

Methods: We utilized the Cochrane Library, PubMed, Web of Science and Embase databases to identify clinical trials evaluating the efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer. The outcomes analyzed were progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR) and the incidence of adverse events (AEs). Subgroup analysis was conducted on the basis of MMR status (deficient, dMMR or proficient, pMMR).

Results: Four trials (582 patients) were included. The pooled ORR was 32.7% [95% confidence interval (CI): 28.9-36.5]. Subgroup analysis revealed an ORR of 48.1% (95% CI: 26.1-70.2) for dMMR group and 33.1% (95% CI: 25.7-40.6) for pMMR group. The pooled DCR was 74.9% (95% CI: 71.3-78.4%). Subgroup analysis revealed a DCR of 81.0% (95% CI: 64.5-97.6) for the dMMR group and 76.3% (95% CI: 66.3-86.3) for the pMMR group. Follow-up was reported in all included studies. The median range time of PFS and OS was 5.3 months-258 days and 17.2 months-not reached, respectively. Regarding safety, the overall pooled proportions of any-grade AE and AEs ≥ grade 3 were 95.8% (95% CI: 89.5-100.0) and 80.2% (95% CI: 59.9-100.0), respectively.

Conclusion: Lenvatinib plus pembrolizumab showed a relevant clinical benefit and significant toxicity in patients with advanced and recurrent endometrial cancer. Further studies encompassing long-term outcomes are warranted.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=522160/, identifier CRD42024522160.

Keywords: endometrial cancer; immunotherapy; lenvatinib; meta-analysis; pembrolizumab.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Endometrial Neoplasms* / drug therapy
  • Endometrial Neoplasms* / mortality
  • Female
  • Humans
  • Neoplasm Recurrence, Local* / drug therapy
  • Phenylurea Compounds* / administration & dosage
  • Phenylurea Compounds* / adverse effects
  • Quinolines* / administration & dosage
  • Quinolines* / adverse effects
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • lenvatinib
  • pembrolizumab
  • Phenylurea Compounds
  • Quinolines

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by Higher Education Key Scientific Research Plan of Henan Province(22A320007) and Higher Education Key Scientific Research Plan of Henan Province(23A310020).