INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line

Br J Cancer. 2023 Apr;128(8):1503-1513. doi: 10.1038/s41416-022-02108-7. Epub 2023 Feb 9.

Abstract

Background: This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC).

Methods: Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75).

Results: The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94-1.35; p = 0.197). Grade 3-5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP).

Conclusions: This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6-12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities.

Clinical trial registration: ClinicalTrials.gov, number NCT01379989.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Carboplatin
  • Carcinoma, Ovarian Epithelial / drug therapy
  • Doxorubicin
  • Female
  • Humans
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / etiology
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / etiology
  • Platinum / therapeutic use
  • Polyethylene Glycols
  • Trabectedin

Substances

  • Carboplatin
  • Trabectedin
  • liposomal doxorubicin
  • Platinum
  • Doxorubicin
  • Polyethylene Glycols

Associated data

  • ClinicalTrials.gov/NCT01379989