Pembrolizumab monotherapy in metastatic triple-negative breast cancer

Given the low response rates observed in the overall population with pretreated triple-negative breast cancer in previous studies of anti-PD-1 or anti-PD-L1 monotherapy,2,5 the primary results of KEYNOTE-119 are unsurprising. Since KEYNOTE-119 was launched, clinical development has focused principally on combinations of chemotherapy and immunotherapy in the first-line setting. The finding that this higher PD-L1 expression threshold might be a predictor of pembrolizumab monotherapy benefit adds to previously observed associations with single drug immunotherapy benefit, including de-novo metastatic disease, absence of previous chemotherapy, normal lactate dehydrogenase, lung or nodal involvement, and absence of liver metastases.2 The hypothesis that checkpoint inhibitor monotherapy is active at higher concentrations of PD-L1 expression, and that at lower concentrations, combination chemoimmunotherapy is required, is analogous to findings in non-small-cell lung cancer. DWC reports consultancy and advisory fees from Agendia, AstraZeneca, Dynamo Therapeutics, Exact Sciences, GlaxoSmithKline, Merck, Novartis, Pfizer, Puma Biotechnology, and Roche; research funding to their institution from GlaxoSmithKline, Pfizer, and Roche; is a member of a trial steering committee for Merck; and holds a holds a patent (US62/675,228) for methods of treating cancers characterized by a high expression level of spindle and kinetochore associated complex subunit 3 (ska3) gene.