No Benefit of Adding Bevacizumab to First-Line Gemcitabine-Docetaxel in Metastatic Uterine Leiomyosarcoma
In a phase III NRG Oncology/Gynecologic Oncology Group (GOG) trial reported in the Journal of Clinical Oncology, Hensley et al found no benefit of adding bevacizumab (Avastin) to first-line gemcitabine-docetaxel in patients with metastatic uterine leiomyosarcoma.
Study Details
In this double-blind trial, 107 patients were randomly assigned between fourth quarter 2009 and second quarter 2013 to receive gemcitabine-docetaxel plus bevacizumab (n = 53) or placebo (n = 54). Treatment consisted of gemcitabine at 900 mg/m2 over 90 minutes followed by bevacizumab at 15 mg/kg or placebo over 90 minutes on day 1 of each cycle and gemcitabine at 900 mg/m2 over 90 minutes followed by docetaxel at 75 mg/m2 over 60 minutes on day 8. Filgrastim (Neupogen) or pegfilgrastim (Neulasta) was given as support. Patients with prior pelvic radiation received gemcitabine at 675 mg/m2 over 70 to 90 minutes on days 1 and 8 and docetaxel at 60 mg/m2 on day 8. The primary endpoint was progression-free survival.
The bevacizumab and placebo groups were generally balanced for age (median, 55 and 56 years), race/ethnicity (68% and 85% white, 23% and 11% African American), Eastern Cooperative Oncology Group performance status (0 for 77% and 70%), prior hormone treatment (none in 94% and 93%), and prior pelvic radiotherapy (21% and 20%).
No Benefit
Accrual was stopped early after interim analysis indicated futility in showing better outcome in the bevacizumab group. Median progression-free survival was 4.2 months in the bevacizumab group vs 6.2 months in the placebo group (hazard ratio [HR] = 1.12, P = .58). Progression-free survival at 12 months was 25% vs 26.4%.
Median overall survival was 23.3 months vs 26.9 months (HR = 1.07, P = .81), and overall survival at 12 months was 71% vs 74.7%. Objective response was observed in 35.8% vs 31.5%, with median duration of response of 8.8 vs 8.6 months.
Toxicity
The addition of bevacizumab to gemcitabine-docetaxel did not result in significantly increased frequency of grade 3 or 4 neutropenia (22% vs 23%), thrombocytopenia (36% vs 28%), or anemia (13% vs 33%). Grade 3 hypertension occurred in 8% vs 0%. Grade 3 and grade 4 thromboembolic events occurred in 6% vs 6% and 4% vs 2%. Grade 3 gastrointestinal hemorrhage occurred in one patient in the placebo group, and grade 3 fistula occurred in one in the bevacizumab group. Any grade 3 or 4 gastrointestinal adverse event occurred in 13% vs 25%.
The investigators concluded: “The addition of bevacizumab to gemcitabine-docetaxel for first-line treatment of metastatic [uterine leiomyosarcoma] failed to improve [progression-free survival, overall survival, or overall response rate]. Gemcitabine-docetaxel remains a standard first-line treatment for [uterine leiomyosarcoma].” They noted: “The failure of bevacizumab to improve any clinical outcome in [uterine leiomyosarcoma] raises the question of whether there is any role for antivascular-directed therapy in this disease.”
Martee L. Hensley, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by National Cancer Institute and NRG Oncology grants. For full disclosures of the study authors, visit jco.ascopubs.org.
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