Platinum-free interval and response to platinum retreatment or lenvatinib/pembrolizumab in patients with recurrent endometrial cancer: A real-world endometrial cancer molecularly targeted therapy consortium cohort study

Gynecol Oncol. 2025 Mar:194:98-104. doi: 10.1016/j.ygyno.2025.02.013. Epub 2025 Feb 21.

Abstract

Objective: We sought to determine the association between platinum-free interval (PFI) and response to retreatment with platinum-based chemotherapy vs lenvatinib/pembrolizumab in patients with recurrent endometrial cancer.

Methods: Endometrial Cancer Molecularly Targeted Therapy (ECMT2) Consortium patients with recurrent disease were included in this retrospective analysis if they received first-line treatment with platinum-based chemotherapy (adjuvant or first recurrence), followed by second-line re-treatment with platinum or lenvatinib/pembrolizumab. PFI was defined as time between date of last platinum to start date of second-line therapy. Patients were stratified according to PFI ≤12 months or > 12 months. Overall response rate (ORR) to second-line treatment was estimated after stratification by PFI.

Results: Of 217 patients, 146 (67 %) underwent retreatment with platinum and 71 (33 %) were treated with lenvatinib/pembrolizumab. 127 (59 %) had PFI ≤12 months, and 84 (39 %) patients had PFI >12 months. Patients treated with platinum had longer PFI than those treated with lenvatinib/pembrolizumab (median PFI 12.9 vs 4.6 months; p < 0.001). ORR was 58 % vs 49 % for platinum vs lenvatinib/pembrolizumab (p = 0.27). For all patients, ORR was 68 % vs 47 % with PFI >12 months and ≤ 12 months, respectively (p = 0.002). At each PFI, ORR was similar regardless of treatment with platinum or lenvatinib/pembrolizumab (PFI ≤12 months ORR 49 % vs 44 % respectively, p = 0.75; PFI >12 months ORR 67 % vs 75 % respectively, p = 0.74).

Conclusion: Longer PFI is associated with improved response to second-line treatment in patients with recurrent endometrial cancer. Despite utilization of PFI for real-world treatment decisions, it was not found to predict response between regimens at any given PFI.

Keywords: Endometrial cancer; Platinum-free interval.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carboplatin / administration & dosage
  • Endometrial Neoplasms* / drug therapy
  • Endometrial Neoplasms* / pathology
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local* / drug therapy
  • Phenylurea Compounds / administration & dosage
  • Quinolines / administration & dosage
  • Retreatment
  • Retrospective Studies

Substances

  • lenvatinib
  • Phenylurea Compounds
  • Quinolines
  • Carboplatin