Estimation of Overall Survival with Subsequent Treatment Effect by Applying Inverse Probability of Censoring Weighting in the LATITUDE Study

Abstract

Background: In the LATITUDE study (ClinicalTrials.gov, NCT01715285), compared with placebos, abiraterone acetate plus prednisone (AAP) with androgen deprivation therapy (ADT) provided significant overall survival (OS) benefit in high-risk metastatic castration-sensitive prostate cancer (mCSPC) patients. It is controversial whether survival benefits would remain if all patients in the placebo group subsequently received life-extending therapies.

Objective: To estimate treatment effect in the case of all patients in the placebo group receiving life-extending subsequent therapies.

Design setting and participants: A post hoc analysis of LATITUDE final-analysis data was carried out (setting and participants have been reported previously).

Intervention: AAP or placebos plus ADT.

Outcome measurements and statistical analysis: We applied the inverse probability of censoring weighting (IPCW) method to represent the situation in which all patients in the placebo group would have received life-extending subsequent therapies. The OS hazard ratio (HR) of AAP versus placebos and associated 95% confidence interval (CI) were estimated using a Cox proportional hazards model.

Results and limitations: Of the 581 eligible patients in the placebo group, 237 (40.8%) did not receive life-extending subsequent therapies. From the unadjusted intention-to-treat analysis, the HR for OS for AAP versus placebos was 0.661 (95% CI 0.564-0.775). Using IPCW to adjust for patients in the placebo group without life-extending subsequent therapies, the HR was 0.732 (95% CI 0.604-0.887). A limitation is a lack of proof that the Cox proportional hazards model for the absence of life-extending subsequent therapy is correctly specified for the IPCW method.

Conclusions: Treatment with AAP exerts OS benefit over placebos in high-risk mCSPC patients, regardless of whether life-extending subsequent therapy is given.

Patient summary: In a previous study, high-risk metastatic castration-sensitive prostate cancer patients who received abiraterone acetate plus prednisone (AAP) with androgen deprivation therapy generally survived longer than those given placebos. The benefit of adding AAP continues regardless of whether life-extending subsequent therapy is given.

Keywords: Abiraterone; Inverse probability of censoring weighting; Metastatic castration-sensitive prostate cancer; Overall survival; Subsequent therapy.