The role of immune checkpoint inhibition in triple negative breast cancer

ABSTRACTIntroduction Immunotherapy has revolutionized cancer treatment, including TNBC, which has limited options of treatment and poor prognosis. ICIs studied in TNBC include pembrolizumab, nivolumab, atezolizumab, and durvalumab. Initial studies exploring ICI monotherapy demonstrated promising yet limited responses. Subsequent studies, KEYNOTE 522 and KEYNOTE 355, which combined ICI with chemotherapy, have resulted in the FDA approval of pembrolizumab in the early-stage and metastatic setting, respectively.Areas covered This article provides a comprehensive review of the role of ICI in the treatment of TNBC. We reviewed the trials that have evaluated ICI monotherapy, dual therapy, ICI in combination with chemotherapy, targeted therapy, vaccines and radiation. Additionally, we reviewed potential biomarkers of response and immune-related adverse events (irAEs). A literature search was conducted via PubMed and ClinicalTrials.gov as of 5 June 2023.Expert opinion Various approaches combining immunotherapy with chemotherapy, targeted therapy, vaccines and radiation have been assessed. Pembrolizumab remains the only ICI approved in both the early stage and mTNBC. The role of adjuvant pembrolizumab in those who achieved pCR after neoadjuvant therapy is being investigated. Combining ICI with PARP inhibitors and radiation shows promise. More research is needed in identifying predictors of response. Monitoring of irAEs remains crucial.KEYWORDS: Atezolizumabbiomarkersimmune checkpoint inhibitorsimmunotherapyirAEPD-L1triple negative breast cancerpembrolizumab Article highlights Immunotherapy has revolutionized cancer treatment, including TNBC, which has limited options of treatment and poor prognosis.ICI monotherapy demonstrated an encouraging yet limited response.The FDA granted accelerated approval to atezolizumab in combination with nab-paclitaxel for PD-L1 positive mTNBC patients based on initial promising data from IMpassion 130, however subsequent disappointing results from the confirmatory IMpassion 131 trial resulted in the withdrawal of this approval. The contradictory results from these similarly designed trials remain unclear.Based on KEYNOTE 355 data pembrolizumab in combination with chemotherapy was approved for PD-L1 positive (CPS ≥ 10) locally recurrent unresectable or mTNBC.Based on the results of KEYNOTE-522, neoadjuvant pembrolizumab in combination with chemotherapy and single-agent adjuvant pembrolizumab is approved for high-risk, early-stage TNBC.More research is needed in identifying predictors of response to ICIs.Although immunotherapy has generally been well tolerated, monitoring of irAEs remains necessary.Declaration of interestK Kalinsky reports consulting fees from Merck, Eli Lilly, Novartis, AstraZeneca, Roche/Genentech, Immunomedics, Seattle Genetics, Oncosec, 4D pharma, Daiichi-Sankyo, Puma Biotechnology, Merasna, Menarini Silicon Biosystems, Myovant Sciences, and Takeda; and grants or funds from Novartis, Ascentage, Roche/Genentech, Eli Lilly, Seattle Genetics, AstraZeneca, and Daiichi-Sankyo.The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Additional informationFundingThis paper was not funded.