Immunotherapy for triple negative breast cancer: How can pathologic responses to experimental drugs in early-stage disease be enhanced?

Abstract

ABSTRACT Introduction The treatment landscape of early triple-negative breast cancer (TNBC) has recently expanded after the Food and Drug Administration (FDA) approval of pembrolizumab in combination with neoadjuvant chemotherapy. The addition of this immune checkpoint inhibitor (ICI) has shown significantly increased pathological complete response (pCR) rate and event-free survival (EFS) in the KEYNOTE-522 phase III trial. Several additional studies are ongoing with the goal of further improving the outcomes and achieving an optimal integration of ICIs in the treatment of TNBC. Areas covered The article examines pCR and survival rates in TNBC. It appraises clinical trials investigating neoadjuvant ICIs for TNBC and the improvement of pCR rates (biomarker-driven escalation of treatment, optimization of chemotherapy backbone, and addition of locoregional treatments or innovative agents). Insights into the role of pCR as a surrogate endpoint and the possibility of enhancing pCR rates for women affected by early TNBC are offered. Expert opinion The pharmacopoeia of early TNBC is growing and becoming more heterogeneous with the advent of ICIs; to enhance the clinical benefit of patients, it is necessary to develop response endpoints that consider the mechanism of action of experimental drugs, to optimize patient selection through validated biomarkers, and to compare the most promising treatment strategies in randomized clinical trials.