Triple negative breast cancer and platinum-based systemic treatment: a meta-analysis and systematic review

BMC Cancer. 2019 Nov 8;19(1):1065. doi: 10.1186/s12885-019-6253-5.

Abstract

Background: Triple negative breast cancer (TNBC) represents 15-20% of breast cancers. Due to its heterogeneity and high rates of relapse, there is a need to optimize treatment efficacy. Platinum chemotherapy is still controversial and currently not recommended as first-line treatment for TNBC. Recent studies have shown promising activity of this regimen. This study was done to evaluate the effect of platinum chemotherapy on pathologic complete response (pCR) after neoadjuvant treatment for early TNBC and progression-free survival (PFS) in metastatic TNBC.

Methods: A systematic search of Pubmed, Embase, Cochrane, Clinical trials databases and hand search were done to identify randomized controlled trials (RCTs) investigating the use of platinum-based chemotherapy in adults with TNBC. Studies were appraised using the Cochrane Collaboration tool. Using the random effects model, pooled Odds ratios (ORs) with 95% confidence intervals (CI) for pCR, and Hazard Ratios (HRs) with 95%CI for PFS were analyzed.

Results: Eleven RCTs were included (N = 2946). Platinum-based chemotherapy showed pCR benefit of 40%vs27% (OR1.75,95% CI 1.46-2.62,p < 0.0001) in the neo-adjuvant setting. Subgroup analysis showed increased pCR rates (44.6%vs27.8%) with platinum plus taxane regimen (p < 0.0001). In metastatic TNBC, three RCTs were analyzed (N = 531), platinum treatment did not show PFS advantage (HR1.16,95%CI 0.90-1.49,p = 0.24).

Conclusion: Platinum chemotherapy is associated with increased pCR rates in TNBC, hence it is a viable option for patients in the neoadjuvant setting. Subgroup analysis showed that the combination of platinum and taxanes (Carboplatin/Paclitaxel) improved pCR. However, no PFS advantage was seen in metastatic TNBC. Given the current conflicting data in metastatic TNBC, further exploration with additional powered studies is needed.

Keywords: Platinum chemotherapy; Triple negative breast cancer.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adult
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • BRCA1 Protein / genetics
  • Bridged-Ring Compounds / therapeutic use*
  • Carboplatin / adverse effects
  • Carboplatin / therapeutic use*
  • Female
  • Humans
  • Mutation
  • Neoadjuvant Therapy / methods*
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / therapeutic use*
  • Paclitaxel / therapeutic use*
  • Progression-Free Survival
  • Randomized Controlled Trials as Topic
  • Taxoids / therapeutic use*
  • Triple Negative Breast Neoplasms / drug therapy*

Substances

  • Antineoplastic Agents, Phytogenic
  • BRCA1 Protein
  • BRCA1 protein, human
  • Bridged-Ring Compounds
  • Organoplatinum Compounds
  • Taxoids
  • taxane
  • Carboplatin
  • Paclitaxel