Adjusting for abiraterone-prednisone cross-over in de novo metastatic castration-sensitive prostate cancer: a post-ho...

INTRODUCTION: PEACE-1 is a 2×2 factorial phase III trial evaluating the impact of abiraterone-prednisone and prostate radiotherapy in patients with de novo metastatic castration-sensitive prostate cancer (mCSPC). Abiraterone-prednisone significantly improved overall survival (OS) (hazard ratio (HR)= 0.82 [95 %CI, 0.69-0.98]). In the control arm, men often received an androgen receptor pathway inhibitor (ARPI) - either abiraterone-prednisone or enzalutamide - after progression to castration-resistant disease. The use of active drug beyond progression may improve post-progression survival and thereby attenuate the estimated benefit of early use of this drug in intention-to-treat analyses. METHODS: This post-hoc analysis applied three statistical methods to estimate an adjusted HR accounting for abiraterone-prednisone use beyond progression: Two-Stage Estimation (TSE), Inverse Probability of Censoring Weighting (IPCW) and Rank-Preserving Structural Failure Time Models (RPSFTM). RESULTS: Among 589 patients randomised to the control arm, 183 received abiraterone-prednisone after disease progression. Compared with patients who did not, these men had higher PSA at diagnosis, higher tumour burden, more bone metastases, and were more likely to have received docetaxel for mCSPC. Experiencing biochemical progression was found to be a risk factor for 2nd line abiraterone use. The HR for OS adjusted by RPSFTM, IPCW, and TSE were 0.79 [0.64-0.98], 0.75 [0.62-0.92], and 0.82 [0.67-0.98], respectively. Sensitivity analyses adjusting for ARPI cross-over (abiraterone-prednisone or enzalutamide) yielded consistent results. CONCLUSIONS: This analysis confirms the survival benefit related to upfront abiraterone-prednisone use for patients with de novo mCSPC.