Are post-docetaxel treatments effective in patients with castration-resistant prostate cancer and performance of 2? A meta-analysis of published trials

BACKGROUND: About 20% of patients with prostate cancer have an ECOG performance status (PS) >= 2 at diagnosis. We investigate if current treatment options for castration-resistant prostate cancer (CRPC) may decrease the risk of death even in patients with ECOG PS of 2. METHODS: PubMed was reviewed for phase III randomized trials in patients with CRPC progressed after docetaxel chemotherapy. Characteristics of each study and the relative hazard ratio (HR) for overall survival and 95% confidence interval (CI) were collected. Summary HR was calculated using random-or fixed-effects models depending on the heterogeneity of included studies. RESULTS: A total of 3,149 patients was available for meta-analysis. In the overall population, the experimental treatments decrease the risk of death by 31% (HR = 0.69; 95% CI: 0.63-0.76; P < 0.001). The activity of experimental treatments was similar in 2,859 patients with ECOG-PS = 0 or 1 with a reduced risk of death of 31% (HR = 0.69; 95% CI: 0.62-0.76). A total of 290 patients (9.2%) had ECOG-PS = 2 and experimental treatments decreased the risk of death by 26% (HR = 0.74; 95% CI: 0.56-0.98; P = 0.035) compared with the controls even in this sub-group. When patients were stratified by type of treatment, the reduction of the risk of death was confirmed for hormonal therapies: abiraterone and enzalutamide (HR = 0.72; 95% CI: 0.52-0.99; P = 0.046), but not for chemotherapy (HR = 0.81; 95% CI: 0.48-1.37; P = 0.43). CONCLUSIONS: We believe this is the first study reporting a benefit in second-line setting for CRPC patients previously treated with docetaxel and poor PS.