Platinum salts in advanced breast cancer : a systematic review and meta-analysis of randomized clinical trials

Background: The interest in platinum salts in breast cancer (BC) therapy has been recently renewed as inhibition of DNA damage response may enhance the effects of DNA-damaging agents in BC tumors with high genomic instability. The present systematic review and meta-analysis of randomized trials were performed to assess the efficacy and safety of therapy with platinum salts in patients with locally advanced or metastatic (hereinafter advanced) BC. Methods: We searched PubMed, EMBASE, SCOPUS, Web of Science, the Cochrane Library, and CINAHL for phase II/III clinical trials that assessed efficacy of platinum-based therapy in patients with advanced BC. Pooled estimates of overall response rate (RR), median progression-free survival (PFS) and overall survival (OS) were computed using random or fixed effects models. Results: Data on 4625 patients from 23 phase II and III trials (11 with cisplatin, 11 with carboplatin, and 1 with either agents respectively) were analyzed. Estimates for RR, PFS, and OS were obtained from 23, 13, and 15 studies, respectively. Although at the cost of significantly increased fatigue, hematological and gastrointestinal toxicity, compared with non-platinum schemas, cisplatin, and carboplatin prolonged OS (HR 0.91; 95 % CI 0.83–1.00, p = 0.04), PFS (HR 0.84; 95 % CI 0.73–0.97, p = 0.01), and RR (HR 1.27; 95 % CI 1.03–1.57, p = 0.03). Conclusions: Despite some limitations of the studies examined, including partial information on hormonal receptor and HER2 status, the use of platinum salts significantly prolonged OS, and PFS of patients with advanced BC with no unexpected toxicity.