In the phase II ALIENOR trial reported in JAMA Oncology, Isabelle Ray-Coquard, MD, and colleagues found that the addition of bevacizumab to paclitaxel did not improve the 6-month progression-free rate among women with relapsed ovarian sex cord–stromal tumors.
Isabelle Ray-Coquard, MD
Study Details
The study, performed in collaboration with the Rare Tumor committee of the Gynecologic Cancer InterGroup, included 60 women with sex cord–stromal tumors that had relapsed after at least one platinum-based chemotherapy from sites in France, Germany, Italy, Japan, and Belgium. Patients were randomly assigned to receive:
- Paclitaxel at 80 mg/m2 on days 1, 8, and 15 every 4 weeks alone for six cycles (n = 32)
- Paclitaxel with bevacizumab at 10 mg/kg on days 1 and 15 every 4 weeks for six cycles followed by maintenance bevacizumab (15 mg/kg every 3 weeks) for up to 1 year or until progression or unacceptable toxicity (n = 28).
Crossover to bevacizumab was permitted after progression during or following paclitaxel alone.
The primary outcome measure was 6-month progression-free rate. The trial used an adaptive Bayesian design, in which the combination group would be superior to the paclitaxel group if the probability of superiority was ≥ 90% at final analysis. Enrollment occurred between 2013 to 2016 and the final analysis database lock was in March 2020.
Six-Month Progression-Free Rate
Median follow-up was 38.9 months.
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 was 57%, which was less than the predefined superiority threshold.
The objective response rate was 25% with paclitaxel alone vs 44% with the combination, with median response durations of 18.0 months vs 15.9 months. Median progression-free survival was 14.7 months vs 14.9 months, with Kaplan-Meier estimated 6-month rates of 72% vs 78%. Kaplan-Meier estimates of overall survival were 94% vs 93% at 1 year and 87% vs 73% at 2 years.
KEY POINTS
- The addition of bevacizumab to paclitaxel did not improve the 6-month progression-free rate.
- The estimated 6-month progression-free rate was 71% with paclitaxel and 72% with paclitaxel/bevacizumab.
Among the 16 patients who crossed over to bevacizumab after progression, median progression-free survival from start of bevacizumab was 6.9 months, with 3 patients having responses of ≥ 12 months.
Adverse Events
The most common adverse events of any grade were hypertension, fatigue, and neuropathy, with bleeding and proteinuria being more common in the combination group. The most common grade ≥ 3 adverse events were hypertension, infection, and neutropenia. No gastrointestinal perforations were observed. Adverse events led to discontinuation of treatment within 6 months in one patient in the combination group.
The investigators concluded, “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…. 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.”
Dr. Ray-Coquard, of Centre Léon Bérard, Université Claude Bernard Lyon, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by Roche. For full disclosures of the study authors, visit jamanetwork.com.
