A phase 3, double-blind, randomized placebo-controlled efficacy and safety study of abiraterone acetate in chemotherapy-naïve patients with mCRPC in China, Malaysia, Thailand and Russia

• Main Authors: Dingwei Ye, Yiran Huang, Fangjian Zhou, Keji Xie, Vsevolod Matveev, Changling Li, Boris Alexeev, Ye Tian, Mingxing Qiu, Hanzhong Li, Tie Zhou, Peter De Porre, Margaret Yu, Vahid Naini, Hongchuan Liang, Zhuli Wu, Yinghao Sun
• Format: Article
• Language: English
• Published: Elsevier 2017-04-01
• Series: Asian Journal of Urology
• Subjects: Abiraterone; Chemotherapy-naïve; Metastatic castration-resistant prostate cancer; Prostate specific antigen; Prednisone
• Online Access: http://www.sciencedirect.com/science/article/pii/S2214388217300164

Objective: This double-blind, placebo-controlled phase 3 study was designed to compare efficacy and safety of abiraterone acetate + prednisone (abiraterone) to prednisone alone in chemotherapy-naïve, asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients from China, Malaysia, Thailand and Russia. Methods: Adult chemotherapy-naïve patients with confirmed prostate adenocarcinoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade 0–1, ongoing androgen deprivation (serum testosterone <50 ng/dL) with prostate specific antigen (PSA) or radiographic progression were randomized to receive abiraterone acetate (1000 mg, QD) + prednisone (5 mg, BID) or placebo + prednisone (5 mg, BID), until disease progression, unacceptable toxicity or consent withdrawal. Primary endpoint was improvements in time to PSA progression (TTPP). Results: Totally, 313 patients were randomized (abiraterone: n = 157; prednisone: n = 156); and baseline characteristics were balanced. At clinical cut-off (median follow-up time: 3.9 months), 80% patients received treatment (abiraterone: n = 138, prednisone: n = 112). Median time to PSA progression was not reached with abiraterone versus 3.8 months for prednisone, attaining 58% reduction in PSA progression risk (HR = 0.418; p < 0.0001). Abiraterone-treated patients had higher confirmed PSA response rate (50% vs. 21%; relative odds = 2.4; p < 0.0001) and were 5 times more likely to achieve radiographic response than prednisone-treated patients (22.9% vs. 4.8%, p = 0.0369). Median survival was not reached. Most common (≥10% abiraterone vs. prednisone-treated) adverse events: bone pain (7% vs. 14%), pain in extremity (6% vs. 12%), arthralgia (10% vs. 8%), back pain (7% vs. 11%), and hypertension (15% vs. 14%). Conclusion: Interim analysis confirmed favorable benefit-to-risk ratio of abiraterone in chemotherapy-naïve men with mCRPC, consistent with global study, thus supporting use of abiraterone in this patient population.