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

Abstract

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.

Keywords: Abiraterone; Chemotherapy-naïve; Metastatic castration-resistant prostate cancer; Prednisone; Prostate specific antigen.

Figure 1

Patient disposition.

Figure 2

Time to prostate specific antigen progression. AA, abiraterone acetate; Obs, observation.

Figure 3

Time to PSA progression based on PCWG2 criteria, forest plot. AA, abiraterone acetate; ECOG, Eastern cooperative oncology group; NE, not estimable; PCWG, prostate cancer working group; PSA, prostate specific antigen.

Figure 4

Waterfall plot of maximum change in PSA from baseline. Shown are the greatest percentage changes in PSA for each patient. A patient must have both baseline and at least one post-baseline assessment to be included in this graph. For patients with more than 100% change, the changes are truncated at 100% in both Y axes. PSA, prostate specific antigen.

Figure 5

Waterfall plot of maximum change in the sum of longest diameter of target lesions from baseline in patients with measurable disease at baseline. Shown are the greatest percentage changes in the sum of longest diameter of target lesions for each patient. A patient must have both baseline and at least one postbaseline assessment to be included in this graph. For patients with more than 100% change, the changes are truncated at 100% on both Y axes.