Platinum is essential in neoadjuvant treatment of triple-negative breast cancer: a network meta-analysis

OBJECTIVE: This study aimed to assess the efficacy and safety of various neoadjuvant regimens for patients diagnosed with early-stage or locally advanced triple-negative breast cancer (TNBC). METHODS: Medline, EMBASE, Cochrane Library, and Web of Science were searched in May 2020 to identify randomized controlled trials (RCTs). Bayesian network meta-analysis (NMA) was performed (Registration: PROSPERO CRD42020223012). RESULTS: A total of 35 RCTs involving 8,424 participants were reviewed, of which 22 RCTs with 5,203 patients were included in this NMA focusing on pathologic complete response (pCR). An anthracycline-taxane-based (AT) regimen combined with a platinum (ATPt) [odds ratio (OR) = 2.04, 95% credible interval (CrI): 1.69, 2.48] regimen, and a docetaxel regimen combined with a carboplatin (TCb; OR = 2.16, 95% CrI: 1.20, 3.91) regimen improved pCR beyond that with AT only. AT and ATPt combined with targeted therapy [including bevacizumab (Bev), veliparib, atezolizumab, or pembrolizumab] also improved pCR. Five RCTs included in this NMA reported serious adverse events (SAEs) or grade ≥ 3 AEs. TCb was associated with fewer grade ≥ 3 AEs than was AT (OR = 0.66, 95% CrI: 0.23, 1.72) alone. In contrast, ATPt, AT + Bev, ATPt + Bev, ATPt + veliparib, and ATPt + pembrolizumab were associated with more SAEs than was AT alone. CONCLUSIONS: In patients with TNBC, platinum-based neoadjuvant regimens ATPt and TCb increase pCR beyond that with AT alone, but TCb appears to be better tolerated than either AT or ATPt. Platinum-based regimens combined with targeted therapies (Bev, PARPi, and PD-1/PD-L1 inhibitor) also improve the pCR rate beyond that with AT alone, but this benefit is accompanied by greater toxicity.