Time to include high-risk early ovarian cancer in randomized phase III trials of advanced ovarian cancer

Abstract

In this issue of Gynecologic Oncology, Bell et al. report on the randomized phase III Gynecologic Oncology Group (GOG) trial of three versus six cycles of adjuvant carboplatin and paclitaxel in early-stage epithelial ovarian carcinoma [ [1] Bell J. Brady M.F. Young R.C. Lage J. Walker J.L. Look K.Y. Rose G.S. Spirtos N.M. Randomized phase III trial of three versus six cycles of adjuvant carboplatin and paclitaxel in early stage epithelial ovarian carcinoma. Gynecol Oncol. 2006; 102: 433-440 Abstract Full Text Full Text PDF Scopus (225) Google Scholar ]. The GOG should be congratulated for completing one of the largest randomized trials in early ovarian cancer, including 457 patients, 427 of whom were eligible. However, although the estimated probability of recurrence within 5 years was 20% for six cycles versus 25% for three cycles, the overall survival in the two arms completely overlapped. This result might have been expected, as the statistical design was very ambitious, i.e., providing an 85% chance of identifying a treatment regimen as active if it reduced the recurrence rate 50% when the type I error was set to 0.05 for a one-tail test. Indeed, in the International Collaborative Ovarian Neoplasm I (ICON1) and European Organisation for Research and Treatment of Cancer–Adjuvant Chemotherapy in Ovarian Neoplasm (EORTC-ACTION) trials, 925 patients were needed to prove that the most active drug in ovarian cancer (platin) significantly improves recurrence-free and overall survival [ [2] International Collaborative Ovarian neoplasm I (ICON1) and European Organisation for Research and Treatment of Cancer collaborators–Adjuvant ChemoTherapy In Ovarian Neoplasm (EORTC-ACTION) International Collaborative Ovarian Neoplasm Trial 1 and Adjuvant ChemoTherapy in Ovarian Neoplasm Trial: Two parallel Randomised Phase III Trials of Adjuvant Chemotherapy in Patients With Early-Stage Ovarian Carcinoma. J Natl Cancer Inst, 2003; 95 (2) 105-12. Google Scholar ]. In this ICON1/EORTC-ACTION trial the recurrence rate was 24% in patients treated with platin-based chemotherapy versus 35% in the no-treatment arm. Overall survival at 5 years improved in the ICON1/EORTC-ACTION trial from 74% in the observation arm to 82% in the chemotherapy arm.