Neo-adjuvant therapy for triple-negative breast cancer: Insights from a network meta-analysis

Background: The best regimen of neo-adjuvant therapy for triple-negative breast cancer (TNBC) is unknown. Recent studies have shown promising data that adding carboplatin or pembrolizumab improves the rate of pathologic complete response (pCR) in TNBC. Therefore, we performed a network meta-analysis to define the overall, most effective, neo-adjuvant systemic therapy for TNBC.

Methods: We searched for studies comparing different neo-adjuvant regimens in patients with TNBC. We performed a network meta-analysis comparing the regimens using the random-effects model. We focused on anthracycline, bevacizumab, pembrolizumab, and platinum salts (Pl). All study regimens contained a taxane. We analyzed the rate of pCR (ypT0/is, N0), and the incidence of febrile neutropenia, grade 3-grade 4 thrombocytopenia, nausea/vomiting, and diarrhea.

Results: We identified a total of 13 randomized control trials for this analysis. We compared ten different classes of regimens. We found that regimens containing Pl were significantly superior to non-PI-containing regimens for the rate of pCR. Similarly, pembrolizumab-containing regimens were associated with significantly higher pCR rates. Regimens containing bevacizumab significantly increased the rate of pCR as well. However, it was equivocal as to whether the addition of Pl to pembrolizumab-containing regimen increases pCR rates. Adding anthracycline into the regimen did not show an improved rate of pCR. In the safety analysis, regimens containing Pl were associated with a significantly higher incidence of febrile neutropenia and grade 3-grade 4 thrombocytopenia. The regimen containing anthracycline plus bevacizumab plus Pl was associated with a higher risk of gastrointestinal adverse events.

Conclusions: For TNBC, regimens containing bevacizumab, pembrolizumab, or Pl are most effective in terms of pCR rates, though it is unclear whether combining all these medications has the greatest efficacy. Additionally, the benefit of using anthracycline in the neo-adjuvant therapy regimen for TNBC is not apparent, which may warrant a further head-to-head comparison.

Keywords: anthracycline; neo-adjuvant; pembrolizumab; platinum salts; triple-negative breast cancer.