Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial

Summary Background The primary analysis of the JGOG 3016 trial showed that a dose-dense paclitaxel and carboplatin regimen signifi cantly improves progression-free and overall survival compared with the conventional regimen as fi rst-line chemotherapy for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer . We report the longterm follow-up results for survival. Methods This randomised controlled trial was done at 85 centres in Japan. Patients with stage II–IV ovarian cancer were randomly assigned to receive conventional treatment (carboplatin area under the curve [AUC] 6 mg/mL per min and paclitaxel 180 mg/m² on day 1) or dose-dense treatment (carboplatin A UC 6 mg/mL per min on day 1 and paclitaxel 80 mg/m² on days 1, 8, and 15). The treatments were repeated every 3 weeks for six cycles; responding patients had three additional cycles. The randomisation was done centrally by telephone or fax, stratifi ed by residual disease, stage, and histological type. The primary endpoint was progression-free survival; overall survival was a secondary endpoint. Long-term information on adverse events was not collected. Effi cacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00226915. Findings 637 patients were enrolled, of whom 631 were analysed (312 assigned to the dose-dense regimen, 319 to the conventional regimen). Median follow-up was 76·8 months (IQR 68·9–85·6). M edian progression-free survival was signifi cantly longer in the dose-dense treatment group than in the conventional treatment group (28·2 months [95% CI 22·3–33·8] vs 17·5 months [15·7–21·7]; hazard ratio [HR] 0·76, 95% CI 0·62–0·91; p=0·0037). Median overall survival was 100·5 months (95% CI 65·2–∞) in the dose-dense treatment group and 62·2 months (52·1–82·6) in the conventional treatment group (HR 0·79, 95% CI 0·63–0·99; p=0·039). Interpretation Dose-dense treatment off ers better survival than conventional treatment and is a potential new standard of care for fi rst-line chemotherapy for patients with advanced epithelial ovarian cancer.