First-line non-cytotoxic therapy in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: a systematic review of ten randomised clinical trials

To systematically evaluate all available treatment options in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC).

We systematically searched PubMed, EMBASE, and the Cochrane libraries up to March 1, 2016 for peer-reviewed publications on randomised clinical trials (RCTs). RCTs were included if progression-free survival (PFS), overall survival (OS), quality of life (QoL), or adverse events (AEs) were quantitatively evaluated. We assessed the risk of bias (RoB) with the Cochrane Collaboration's tool and graded the evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group's approach.

We included 25 articles, reporting on ten unique RCTs describing seven different comparisons. In one RCT, a prolonged OS and PFS (high quality) were found with abiraterone and prednisone compared to placebo plus prednisone. In one RCT, a prolonged OS and PFS (high quality) were found with enzalutamide compared to placebo. In two RCTs, a prolonged OS (high and moderate quality) was found with (223) radium compared to placebo, but its effect on PFS is unknown. In three RCTs, a prolonged OS (moderate quality) was found with sipuleucel-T compared to placebo, but no prolonged PFS (low quality). In one RCT a prolonged PFS (high quality) was found with orteronel compared to placebo, but no prolonged OS (moderate quality). In one RCT, a prolonged OS (moderate quality) was found with bicalutamide compared to placebo, but its effect on PFS is unknown. In one study, a prolonged PFS (high quality) was found with enzalutamide compared to bicalutamide, but its effect on OS is unknown.

The best evidence was found for abiraterone and enzalutamide for effective prolongation of PFS and OS to treat chemotherapy-naive mCRPC patients. However, taking both QoL and AEs into consideration, other treatment modalities could be considered for individual patients. This article is protected by copyright. All rights reserved.

BJU international. 2017 Jan 06 [Epub ahead of print]

Michiel H F Poorthuis, Robin W M Vernooij, R Jeroen A van Moorselaar, Theo M de Reijke

Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands., Department of Urology, VU University Medical Center, Amsterdam, The Netherlands., Department of Urology, Academic Medical Center, Amsterdam, The Netherlands.