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Background: AA,a CYP17 inhibitor,prolongs the lives of men with progressive pre-or post-chemotherapy treated mCRPC with a favorable safety profile(Rathkopf et al.ASCO-GU 2013.Abstr 5).This post hoc analysis examines the safety and tolerability of long-term treatment(≥ 24 mos)in study COU-AA-302.Methods: 1,088 pts were randomized 1:1 to AA 1000 mg + P 5 mg po BID vs placebo + P.Co-primary endpoints were radiographic progression-free survival(rPFS)and OS.Median times with 95%CI of the end points were estimated using the Kaplan-Meier(KM)method.Post hoc analysis of adverse events(AEs)was performed at pre-specified interim analysis(IA3)(55%OS events).Results: At a median follow-up = 27.1 mos(IA3): rPFS HR(95%CI)= 0.53(0.45,0.62),p < 0.0001 and OS was improved over P [0.79(0.66,0.96),p = 0.0151]; the latter did not reach the pre-specified efficacy boundary(p = 0.0035).All secondary endpoints favored the AA arm(Rathkopf et al.ASCO-GU 2013.Abstr 5).The incidence rate of selected AEs by duration of exposure is shown below(Table).There was no clinically relevant increase in the incidence rate of AEs with longer exposure using AA + P versus P alone; although pts on treatment for ≥ 24 mos may have had greater tolerability.The percentage of patients who came off study due to an AE was 8%(AA)versus 6%(P).Conclusions: The updated IA3 of COU-AA-302 in pts without prior chemotherapy confirms the delay in progression and prolongation of life with a favorable safety profile including pts treated for ≥ 24 mos with AA + P or P.