Adjusting Overall Survival Estimates for Treatment Switching in Metastatic, Castration-Sensitive Prostate Cancer: Results from the LATITUDE Study.

Abstract

BackgroundLATITUDE was the first phase 3 trial examining the survival benefit of adding abiraterone acetate (AA) + prednisone (P) to androgen-deprivation therapy (ADT) in newly diagnosed metastatic, castration-sensitive prostate cancer (mCSPC). Due to significant improvement in overall survival after the first interim analysis, patients in the placebos + ADT arm could switch to AA + P + ADT during an open-label extension. As in other studies where switching is allowed, statistical adjustments are needed to assess the real benefit of new drugs.Patients and MethodsThis was a post hoc analysis to estimate the true survival benefit of AA + P + ADT in patients with newly diagnosed mCSPC by applying statistical adjustments commonly used to adjust for treatment switching.ResultsOf 112 patients still receiving placebos + ADT at the first interim analysis, 72 switched to AA + P + ADT during the open-label extension. Final analysis was conducted after median follow-up of 51.8 months. Compared to the placebos + ADT arm, the risk of death in the AA + P + ADT arm was 34% lower [hazard ratio (HR) = 0.663 (95% confidence interval 0.566–0.778)] by unadjusted intent-to-treat analysis, 37% lower [HR = 0.629 (95% confidence interval 0.526–0.753)] by rank preserving structure failure time modeling, and 38% lower [HR = 0.616 (95% confidence interval 0.524–0.724)] by inverse probability of censoring weights.ConclusionsAnalyses adjusting for treatment switching using two different statistical approaches confirm the improved survival benefit of adding AA + P to ADT in patients with newly diagnosed mCSPC.Trial RegistrationClinicalTrials.gov identifier NCT01715285.Electronic supplementary materialThe online version of this article (10.1007/s11523-019-00685-x) contains supplementary material, which is available to authorized users.