Immunotherapy addition to neoadjuvant chemotherapy for early triple negative breast cancer: A systematic review and meta-analysis of randomized clinical trials

Abstract

Importance: Several randomized trials of neoadjuvant chemo-immunotherapy in early triple negative breast cancer (TNBC) have been recently reported, showing conflicting results.

Methods: We systematically searched PubMed, Cochrane CENTRAL, Embase and key oncological meetings for trials of neoadjuvant chemo-immunotherapy in TNBC. The primary endpoint was pCR, with sub-analyses based on PD-L1 expression and risk of relapse.

Results: Five randomized trials enrolling 1496 TNBC patients were included. We observed a statistically significant association between PD1/PD-L1 blockade addition and pCR (SOR = 1.72, 95 %CI: 1.22-2.42). The benefit was significant in the PD-L1 positive subgroup (SOR = 1.65; 95 %CI: 1.06-2.57). pCR was also significantly increased in the high-risk subgroup (SOR = 2.39; 95 %CI: 1.09-5.22), when restricting to patients receiving an anthracycline-based NACT. We found no significant association between immunotherapy addition and toxicity, and no evidence of publication bias.

Conclusions: The addition of PD1/PD-L1 blockade to NACT significantly improves pCR rates in TNBC patients, particularly in patients at high-risk of relapse.

Keywords: Atezolizumab; Durvalumab; Immune-checkpoint inhibitor; Neoadjuvant; Pembrolizumab; Triple-negative breast cancer.