ICON2: randomised trial of single-agent carboplatin against three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) in women with ovarian cancer

Background A series of meta-analyses of randomised controlled trials raised the question of whether the three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) was more or less effective than optimal-dose single-agent carboplatin for women with advanced ovarian cancer. Methods We carried out an international, multicentre, randomised trial to compare CAP with single-agent carboplatin in women with ovarian cancer requiring chemotherapy. 1526 patients were entered from 132 centres in nine countries. Analyses were by intention to treat. Findings 728 patients have died (368/766 allocated CAP vs 360/760 allocated carboplatin) and the survival curves show no evidence of a difference between CAP and carboplatin (hazard ratio 1·00 [95% CI 0·86–1·16]; p=0·98). The results indicate a median survival of 33 months and a 2-year survival of 60% for both groups. We found no evidence that CAP or carboplatin were more or less effective in different subgroups defined by age, stage, residual disease, differentiation, histology, and coordinating centre. CAP was substantially more toxic than carboplatin, causing more alopecia, leucopenia, and nausea. More thrombocytopenia occurred with carboplatin. Interpretation Single-agent carboplatin, with the dose calculated by the area-under-the-curve method, is a safe, effective, and appropriate standard of treatment for women with advanced ovarian cancer.