Effect of Weekly Paclitaxel with or without Bevacizumab on Progression-Free Rate among Patients with Relapsed Ovarian Sex Cord-Stromal Tumors: The ALIENOR/ENGOT-ov7 Randomized Clinical Trial

Isabelle Ray-Coquard, Philipp Harter, Domenica Lorusso, Cécile Dalban, Ignace Vergote, Keiichi Fujiwara, Laurence Gladieff, Hans Joachim Lück, Anne Floquet, Annick Chevalier-Place, Andreas Schnelzer, Sandro Pignata, Frédéric Selle, Jalid Sehouli, Fabien Brocard, Giorgia Mangili, Patricia Pautier, Ugo De Giorgi, Magali Provansal, Pierre Etienne Heudel

Research output: Contribution to journalArticlepeer-review

Abstract

Importance: To our knowledge, this is the first randomized trial in sex cord-stromal tumors, and it establishes weekly paclitaxel as standard-of-care therapy after platinum-based therapy in this setting. Objective: To determine the efficacy of weekly paclitaxel with or without bevacizumab as treatment for relapsed sex cord-stromal tumors and evaluate whether the addition of bevacizumab to weekly paclitaxel improves 6-month progression-free rate. Design, Setting, and Participants: This open-label, academic, international, randomized phase 2 trial (ALIENOR) was conducted at 28 referral centers in France, Germany, Italy, Japan, and Belgium in collaboration with the Rare Tumor committee of the Gynecologic Cancer InterGroup and used an adaptive bayesian design. It included 60 women with sex cord-stromal tumors that had relapsed after at least 1 platinum-based chemotherapy. Enrollment occurred from 2013 to 2016, and the final analysis database lock was on March 27, 2020 (median follow-up, 38.9 months). Interventions: Participants were randomized to receive either paclitaxel (80 mg/m2, days 1, 8, and 15 every 4 weeks) alone or paclitaxel with bevacizumab (10 mg/kg, every 2 weeks) for 6 cycles followed by maintenance bevacizumab (15 mg/kg, every 3 weeks) for up to 1 year or until progression or unacceptable toxicity. Crossover to bevacizumab was permitted after progression during or following paclitaxel alone. Main Outcomes and Measures: Six-month progression-free rate. Results: Sixty patients (predominantly with granulosa cell tumors) were randomized, 32 to receive single-agent paclitaxel (median [interquartile range] age at inclusion, 60 [53-64] years) and 28 to receive paclitaxel-bevacizumab (median [interquartile range] age at inclusion, 55 [47-61] years; 1 did not receive treatment). The estimated 6-month progression-free rate was 71% (95% credible interval, 55%-84%) with paclitaxel alone and 72% (95% credible interval, 55%-87%) with paclitaxel-bevacizumab. The bayesian estimate for the probability that the 6-month progression-free rate distribution was higher with the combination than with paclitaxel alone was 57%, less than the predefined superiority threshold. The objective response rate increased from 25% (95% CI, 12%-43%) to 44% (95% CI, 26%-65%) with the addition of bevacizumab. One patient discontinued combination therapy within 6 months because of toxicity. Conclusions and Relevance: Weekly paclitaxel is a new option for relapsed sex cord-stromal tumors. In this international randomized clinical trial of patients with relapsed sex cord-stromal tumors unsuitable for surgery, adding bevacizumab to weekly paclitaxel does not improve clinical benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT01770301.

Original languageEnglish
Pages (from-to)1923-1930
Number of pages8
JournalJAMA oncology
Volume6
Issue number12
DOIs
Publication statusPublished - Dec 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Effect of Weekly Paclitaxel with or without Bevacizumab on Progression-Free Rate among Patients with Relapsed Ovarian Sex Cord-Stromal Tumors: The ALIENOR/ENGOT-ov7 Randomized Clinical Trial'. Together they form a unique fingerprint.

Cite this