Abstract ES10-2: Immune therapy in the (neo) adjuvant setting

Abstract

Abstract Historically, the treatment of early-stage triple negative breast cancer (TNBC) has hinged on the administration of conventional cytotoxics. However, the curative-intent treatment landscape has recently evolved with the successful development of checkpoint blockade inhibitor (CPI) strategies. Specifically, on July 27, 2021, the United States FDA approved the PD-1 directed antibody, pembrolizumab, for high-risk early-stage TNBC together with chemotherapy as neoadjuvant treatment and then continued as a single agent as adjuvant treatment after surgery based on the results of the randomized, phase 3 KEYNOTE-522 study. In this study, the addition of pembrolizumab to a platinum-, taxane- and anthracycline-based regimen conferred an absolute 13.6% improvement in pathologic complete response (pCR) in the intention-to-treat population at the first interim analysis, with benefits observed irrespective of PD-L1 status. Although the absolute benefit subsequently decreased to 7.5% at the third interim analysis, the event free survival (EFS) benefit was maintained. In fact, with a median follow-up of 39.1 months at the fourth interim analysis, the EFS was 15.7% versus 23.8% (HR 0.63, p= 0.00031) in favor of the CPI containing regimen. The Geparnuevo study, a modestly powered study in which randomized patients with early stage TNBC to receive neoadjuvant chemotherapy with or without durvalumab, a PD-L1 targeting CPI, did not meet its pCR primary endpoint; however, in a recent update reporting on secondary endpoints, improvements in invasive disease free survival (85.6% vs 77.2%), distant disease free survival (91.7% vs 78.4%) and overall survival (95.2% vs 83.5%) were reported in favor of the CPI-containing regimen. EFS data from the IMpassion031 study of neoadjuvant chemotherapy with or without the PD-L1 targeting CPI, atezolizumab, are anticipated after an absolute 16.5% improvement in pCR was reported in the intention-to-treat population with the addition of the CPI, with benefits observed regardless of PD-L1 status. Studies evaluating the role of CPI strategies in the adjuvant setting are also underway. For example, pembrolizumab is being evaluated as monotherapy for patients with residual TNBC after neoadjuvant chemotherapy in the SWOG 1418 study and atezolizumab is being administered with adjuvant chemotherapy after upfront surgery for early-stage TNBC in the IMpassion030/ALEXANDRA study. Studies evaluating curative-intent CPI and targeted therapies and/or local therapies are underway or planned. Available data, current controversies and future directions will be discussed. Citation Format: H McArthur. Immune therapy in the (neo) adjuvant setting [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES10-2.