Cabazitaxel with abiraterone versus abiraterone alone randomized trial for extensive disease following docetaxel: The CHAARTED2 trial of the ECOG-ACRIN Cancer Research Group (EA8153).

LBA5000 Background: The E3805 (CHAARTED) trial showed a significant survival benefit from early treatment with chemohormonal therapy (ADT + Docetaxel) in patients (pts) with high-volume metastatic hormone-sensitive prostate cancer (HSPC). However, most pts will develop castration-resistant disease (CRPC) and will require additional systemic therapy. We hypothesized that additional treatment with chemohormonal therapy in the CRPC setting will improve outcomes. Methods: EA8153 (CHAARTED2) is a prospective randomized phase II open label trial. Two hundred twenty-three (223) pts with metastatic CRPC previously treated with ADT + docetaxel for HSPC were randomized (1:1) to abiraterone/prednisone plus cabazitaxel 25 mg/m 2 for up to 6 cycles (n = 111) or abiraterone/prednisone alone (n = 112). Stratification factors included ECOG performance status (PS) of 0 vs. 1-2, time from initiation of ADT to development of CRPC of 12 months, and presence vs. absence of visceral metastases. The primary trial endpoint is progression-free survival (PFS), defined as time from randomization to radiographic progression, symptomatic deterioration requiring discontinuation of treatment, or death. Key secondary endpoints include time to PSA progression (TTPP), overall survival (OS), and safety. Results: After a median follow-up of 47.3 (0-61.2) months, median PFS was longer for the cabazitaxel + abiraterone/prednisone arm vs. abiraterone/prednisone alone arm (14.9 months 95% CI 9.9-18.6 vs. 9.9 months 95% CI, 7.0-12.6, P = 0.049; hazard ratio HR 0.73, 80% CI 0.59-0.90). The advantage with the combination was more pronounced in patients 3 side effects were noted in the combination arm, as expected from use of cabazitaxel. Conclusions: The addition of cabazitaxel to abiraterone/prednisone significantly prolonged PFS in patients with metastatic CRPC who previously received ADT + docetaxel for HSPC compared to abiraterone/prednisone alone. No significant OS difference was noted between the two arms, but the study was not powered for this endpoint. Clinical trial: NCT03419234. Support: CA180820, CA180794, CA180799, CA180802; and Genzyme Corporation, a subsidiary of Sanofi S.A. Clinical trial information: NCT03419234 .