A subgroup analysis of the TROPIC trial exploring reason for discontinuation of prior docetaxel and survival outcome of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC).

4526^ Background: The Phase III TROPIC trial showed that cabazitaxel plus prednisone (CbzP) significantly improved overall survival (OS) compared with mitoxantrone plus prednisone (MP) in men with mCRPC whose disease progressed during or after treatment with a docetaxel regimen (Lancet 2010; 376:1147-54). We conducted a post hoc analysis of TROPIC to assess whether the survival benefit of CbzP was maintained in subgroups defined by the reason for discontinuation of prior docetaxel. METHODS The analysis included the 755 men randomized to receive either CbzP (n=378) or MP (n=377). Reason for discontinuation of prior docetaxel was documented in case report forms (disease progression, adverse events, completed treatment, other reasons). The Kaplan-Meier method was used to analyze OS, which was defined from the time of randomization to death (any cause). Unadjusted hazard ratios (HR) and 95% confidence intervals (CI) were calculated using the Cox proportional hazards model. RESULTS The majority of patients were randomized to TROPIC within 6 months of last docetaxel dose. Progression occurred during or within 3 months of last docetaxel dose in 72% of CbzP and 76% of MP patients. The proportion of randomized patients that discontinued prior docetaxel due to disease progression was similar (63% CbzP; 61% MP). In this subgroup, the median OS was 13.8 months with CbzP vs. 10.9 months with MP (HR 0.70; 95% CI 0.57-0.87). The survival benefit of CbzP over MP was also evident in the 286 patients (CbzP: n=139; MP: n=147) who discontinued prior docetaxel for a reason other than disease progression, with a median OS of 18.0 months with CbzP vs. 15.6 months with MP (HR 0.63; 95% CI 0.46-0.85). Analysis of the small subgroup of patients (CbzP: n=22; MP: n=26) who discontinued prior docetaxel due to an adverse event suggests a consistent improvement in OS (median 16.0 months CbzP; 14.8 months MP [HR 0.63; 95% CI 0.30-1.33]). CONCLUSIONS This post hoc analysis suggests that the survival benefit of CbzP over MP in men with mCRPC is maintained irrespective of whether prior docetaxel treatment was discontinued due to disease progression.