Outcomes in patients with liver or lung metastatic castration-resistant prostate cancer (mCRPC) treated with the androgen receptor inhibitor enzalutamide: Results from the phase III AFFIRM trial.

Abstract

5065 Background: Enzalutamide (ENZA) inhibits multiple steps in the androgen receptor signaling pathway (Tran et al, Science. 2009;324:787). The phase III AFFIRM trial demonstrated that ENZA increased median overall survival (OS) by 4.8 months (P <0.001, HR 0.63) vs placebo (PBO) in post-docetaxel mCRPC patients (pts) (Scher et al, NEJM 2012; 367:1187). Here we assess the effect of ENZA on outcomes in pts with liver or lung metastases in the AFFIRM trial. Methods: The AFFIRM trial was a phase III multinational, randomized, double-blind study in post-docetaxel mCRPC pts. Randomization was 2:1 to ENZA 160 mg/day or PBO, stratified by baseline ECOG and mean pain score. The primary endpoint was overall survival (OS). Radiographic progression-free survival (rPFS) was a key secondary endpoint. PSA response defined as a decline of ≥50% compared to baseline, and soft tissue objective response per RECIST 1.1 were also assessed and reported here. Results: Pts with liver mCRPC comprised 11.5% (92/800) of ENZA pts and 8.5% (34/399) of PBO pts. Pts with lung mCRPC comprised 15.3% (122/800) of ENZA pts and 14.8% (59/399) of PBO pts. The median OS for patients with liver and/or lung mCRPC in the AFFIRM trial was 11.4 months (ENZA: 13.4 months; PBO: 9.5 months). Improved outcomes with ENZA treatment were observed in both liver and lung mCRPC pts. Conclusions: In the phase III AFFIRM trial, pts with lung mCRPC had higher median OS than pts with liver mCRPC. ENZA resulted in higher response rates in both liver and lung mCRPC pts. OS and rPFS were also improved in both pt groups treated with ENZA. Clinical trial information: NCT00974311. [Table: see text]