Is the fatigue an adverse event of the second generation of hormonal therapy? Data from a literature-based meta-analysis.

New hormonal therapies have enriched the therapeutic armamentarium for patients with castration-resistant prostate cancer (CRPC). Fatigue is one of the most common adverse events registered in phase III trials of these new drugs. The aim of this article is to perform a meta-analysis based on all available literature data focused on the risk rate (RR) of fatigue from new hormonal agent-based therapy in patients with CRPC. A total of 11,751 cases were included from 11 randomized trials. The analysis revealed that the second generation of hormonal therapies increased the RR of any-grade fatigue (RR = 1.27) and grade 3-4 fatigue (RR = 1.25). This last adverse event was always higher in a pre-chemotherapy setting. In conclusion, given the limitations of a literature-based study, rather than a meta-analysis based on individual patients' data, our study confirmed the increase in the RR for any-grade and grade 3-4 fatigue during the second generation of hormonal therapies, with particular attention being paid to grade 3-4 in the pre-chemotherapy setting of the disease.