Systemic Treatment for Metastatic Hormone Sensitive Prostate Cancer: A Comprehensive Meta-Analysis Evaluating Efficacy and Safety in Specific Sub-Groups of Patients

Abstract

Background and objectives: Several systemic treatments are available for metastatic hormone sensitive prostate cancer (mHSPC) including docetaxel (D), abiraterone and prednisone (A + P) and new anti-androgens (NA). In our study we performed a systematic review and meta-analysis assessing efficacy outcomes (survival and radiological-free survival), safety and survival on specific subgroups of patients.

Methods: Outcomes of interest were: (i) Risk of death, biochemical and radiological progression among all patients. (ii) Risk of death according to different pathological/clinical features. (iii) Evaluation of the relative risk (RR) and risk difference of serious toxicity defined as adverse events (AEs) with grade ≥ 3 specific AEs. Hazard ratios (HRs) and RR were measures adopted for endpoints 1-3.

Results: Overall, eight randomized trials were included in meta-analysis for a total of 9987 patients. Administration of D, A + P and NA resulted in improved overall survival (OS) and radiological progression-free survival (rPFS). Survival benefit was not confirmed in patients receiving NA and previously exposed to docetaxel (HR 0.948, 95% CI 0.671-1.338). Patients with visceral metastases and high lactate dehydrogenase (LDH) did not benefit from NA treatment, while it seems that patients with low Gleason score do not benefit from A + P. NA showed the more favorable safety profile.

Conclusion: NA may not provide survival benefit when adopted subsequently or in concomitant to D. Specific subgroups of patients may benefit more from A + P, D or NA. Safety profiles significantly differ among agents evaluated.