Enzalutamide (E) Re-Challenge As Second-Line in Metastatic Castration-Resistant Prostate Cancer (mcrpc) Patients (pts) Treated with First-Line Enzalutamide + Docetaxel (D): Preliminary Results of a Post-Progression Analysis of CHEIRON Trial.

123 Background: CHEIRON trial was a phase II study which randomized previously untreated mCRPC pts to receive D 75 mg/m2 IV d1 q3w for 8 courses alone or plus E 160 mg PO daily. As per protocol, E was administered in experimental arm for only 24 wks until D conclusion. The study met its primary endpoint since the rate of pts without disease progression at 6 mos was significantly higher in DE arm compared to D arm (89.1% vs 72.8%; p = 0.002). The clinicians were asked to consider an E re-challenge as first post-progression treatment for those pts without disease progression at the chemotherapy end in the experimental arm. We presented the preliminary analysis of E activity in post-progression setting of CHEIRON DE arm. Methods: We evaluated all patients enrolled in the experimental arm, focusing on pts who received E as first post-progression treatment. We collected data concerning the treatment duration and disease control and compared the outcomes of pts treated with E re-challenge with those of pts who received other treatments at the time of first progression after experimental therapy. Results: Among the 120 pts who received DE experimental arm, 101 did not show a disease progression and 82 received a second-line active treatment: 54 (66%) were treated with E, the other received abiraterone (10 pts), cabazitaxel (13 pts), and radium 223 (5 pts). The median interval between the end of DE and the start of E re-challenge was 7.6 mos (range 0.9-18.4 mos). At a median follow-up of 15.5 mos, the median duration of E re-challenge was 9.8 mos (range 1.9-30.9) with 22 pts still on treatment. Pts who received E rechallenge showed a median progression free survival of 11.4 mos which was significantly longer compared to 4.5 mos showed in pts who received other treatments (p < 0.0001). The median overall survival was 20.4 mos and 12.3 mos, respectively (p = NS). Conclusions: In pts who received first-line DE in the CHEIRON trial, the reintroduction of E after a per-protocol discontinuation demonstrated to be feasible, with a prolonged disease control compared to the other post-progression therapeutic options. Clinical trial information: NCT02453009.