The Efficacy and Safety of Folate Receptor α-Targeted Antibody-Drug Conjugate Therapy in Patients With High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers: A Systematic Review and Meta-Analysis

Cancer Med. 2024 Nov;13(21):e70392. doi: 10.1002/cam4.70392.

Abstract

Background: Antibody-drug conjugates (ADC) have emerged as a highly promising systemic option in the treatment of recurrent ovarian cancer. The present study aimed to evaluate the treatment efficacy of folate receptor α (FRα)-targeting ADCs, associated treatment-related adverse events (TRAEs), and their impact on treatment safety.

Methods: We conducted an electronic search to identify prospective trials of single-agent ADCs targeting FRα and those combined with chemotherapy in recurrent ovarian cancer. Information regarding the objective response rate (ORR) and TRAEs was collectively analyzed, and differences in subgroups based on FRα receptor expression levels were investigated. The protocol was registered with PROSPERO (CRD42023491151).

Results: Ten studies with a total of 940 patients (859 treated with Mirvetuximab soravtansine-gynx (MIRV)), 45 with Farletuzumab Ecteribulin (MORAb-202), and 36 with Luveltamab Tazevibulin (STRO-002) were included in this meta-analysis. Based on the pooled data, the ORR of the entire cohort was 37% (95% CI: 0.30-0.43), while that of the high-FRα expression group was 34% (95% CI: 0.26-0.42). The incidence of grade ≥ 3 adverse events was 27% (95% CI: 0.19-0.36).

Conclusion: FRα-targeting ADCs, including MIRV, demonstrated definite efficacy and good safety as novel choices for second-line and beyond treatment of advanced or recurrent ovarian cancer. Patients with high FRα expression showed ORR and PFS benefits similar to those in the overall cohort.

Keywords: adverse event; antibody‐drug conjugate; folate receptor alpha; mirvetuximab soravtansine; ovarian cancer.

Publication types

  • Systematic Review
  • Meta-Analysis

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Carcinoma, Ovarian Epithelial* / drug therapy
  • Carcinoma, Ovarian Epithelial* / pathology
  • Fallopian Tube Neoplasms* / drug therapy
  • Fallopian Tube Neoplasms* / pathology
  • Female
  • Folate Receptor 1* / antagonists & inhibitors
  • Folate Receptor 1* / metabolism
  • Humans
  • Immunoconjugates* / adverse effects
  • Immunoconjugates* / therapeutic use
  • Maytansine / adverse effects
  • Maytansine / analogs & derivatives
  • Maytansine / therapeutic use
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / pathology
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / pathology
  • Peritoneal Neoplasms* / drug therapy
  • Peritoneal Neoplasms* / pathology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • farletuzumab
  • Folate Receptor 1
  • Immunoconjugates
  • Maytansine
  • mirvetuximab soravtansine