Weekly dose-dense paclitaxel did not provide a progression-free survival benefit over every-3-week paclitaxel in combination with carboplatin and with or without elective bevacizumab (Avastin) in patients with previously untreated ovarian cancer, according to the results of the phase III GOG-0262 trial. A benefit of weekly paclitaxel was observed in the minority of patients who did not receive bevacizumab. John K. Chan, MD, of the California Pacific–Palo Alto Medical Foundation, Sutter Cancer Research Institute, San Francisco, and colleagues reported their findings in The New England Journal of Medicine.
In this open-label trial, 692 patients from 209 sites in the United States, Canada, and South Korea were randomly assigned between September 2010 and February 2012 to receive paclitaxel at 80 mg/m2 every week (n = 346) or 175 mg/m2 every 3 weeks (n = 346) in addition to carboplatin (area under the curve = 6) for six cycles after being prospectively stratified according to whether they elected to receive bevacizumab. Bevacizumab was given at 15 mg/kg every 21 days beginning with the second cycle of therapy and continued until disease progression or unacceptable toxicity.
Eligible patients had previously untreated, incompletely resected stage III or any stage IV epithelial ovarian, fallopian tube, or primary peritoneal cancer; after closure of a competing trial, patients with stage II or III disease with no residual lesions > 1cm were also included. In addition, patients who opted for neoadjuvant therapy were permitted entry. The primary endpoint was progression-free survival on an intent-to-treat analysis.
Bevacizumab was received by 84% of patients in both groups. For the weekly vs every-3-week groups: 45% and 46% were aged < 60 years; disease stage was II in 2% and 3%, III in 70% and 64%, and IV in 28% and 33%; the site of origin was the ovary in 78% and 81%; 63% and 64% had gross residual disease; 87% and 89% had serous histology; and 13% in each group elected to receive neoadjuvant therapy followed by interval cytoreductive therapy.
Median follow-up was 28 months. Median progression-free survival was 14.7 months with weekly paclitaxel vs 14.0 months with every-3-week paclitaxel (hazard ratio [HR] = 0.89, P = .18). Median progression-free survival was 14.2 vs 10.3 months among patients who did not receive bevacizumab (HR = 0.62, P = .03) and 14.9 vs 14.7 months among those who received bevacizumab (HR = 0.99, P = .60; P = .047 for interaction). The investigators noted that this difference in outcome did not appear to reflect imbalances in known prognostic factors.
Grade ≥ 3 anemia was more common in the weekly paclitaxel group (36% vs 16%, P < .001). Grade ≥ 3 neutropenia was more common in the every-3-week group (72% vs 83%, P < .001). Patients in the weekly group were more likely to receive cytokine treatment (30% vs 22%, P = 0.02) and red blood cell transfusion (55% vs 23%, P < .001). Grade ≥ 2 sensory neuropathy occurred in 26% vs 18% of patients (P = 0.01), with no difference in grade ≥ 3 neuropathy. Six deaths in the weekly group and 8 deaths in the every-3-week group were considered possibly related to study treatment.
The investigators concluded: “Overall, weekly paclitaxel, as compared with paclitaxel administered every 3 weeks, did not prolong progression-free survival among patients with ovarian cancer.”
The study was funded by the National Cancer Institute and Genentech.
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