Overall survival results of ICON6: A trial of chemotherapy and cediranib in relapsed ovarian cancer.

5506 Background: ICON6 is a three-arm double-blind, placebo-controlled phase 3 trial of cediranib in platinum-sensitive relapsed ovarian cancer (NCT00532194). The primary analysis (Ledermann et al Lancet 2016) showed a significant (p < 0.0001), 2.3 month extension in progression-free survival (PFS) using cediranib with chemotherapy and as maintenance compared to chemotherapy and placebo. We present the final overall survival (OS) results. Methods: The trial was originally designed to recruit 2000 patients with OS as the primary endpoint. AstraZeneca discontinued cediranib development in Sep 2011, leading to an unplanned redesign prior to analysis. The sample size was reduced and primary outcome became PFS, comparing two arms, placebo (A) to cediranib given with chemotherapy and as maintenance (C). In arm B cediranib was given with chemotherapy followed by placebo maintenance. Analysis of PFS was performed on a sample size of 456 patients receiving a 20mg dose of cediranib. At the primary analysis, 52% patients had died; this mature OS analysis was performed after 85% patients died. Results: The OS analysis was performed at a median 25.6 months follow up; 102/118 (86%) died in A and 140/164 (85%) in C. In A the median survival was 19.9 months (95% CI: 17.4, 26.5) and in C 27.3 months (24.8, 33.0). Using the logrank test the Hazard Ratio estimate was 0.85 (0.66, 1.10) in favour of cediranib (p = 0.21). Evidence of non-proportionality of the survival curves was observed (p = 0.0029), so we measured the Restricted Mean Survival Time as an alternative to the median. Over 6 years, there was a 4.8 month (-0.1, 9.8) increase in time to death in C compared to A, from 29.4 to 34.2 months. The mean for arm B (32.0 months) was consistent with a benefit of increased use of cediranib. Conclusions: Cediranib has demonstrated a significant effect in increasing PFS. The mature survival analysis (85%) shows an improvement in median OS of 7.4 months, and an incremental benefit with increased cediranib use. The previously published significant PFS benefit coupled with the increase in OS highlights the potential value of cediranib in platinum-sensitive recurrent ovarian cancer. Further exploration of cediranib in this setting is underway. Clinical trial information: NCT00532194.