Department of Medicine, University of Chicago, Chicago, USA.
Expert Opin Investig Drugs. 2022 Jun;31(6):531-548. doi: 10.1080/13543784.2022.1986002. Epub 2021 Oct 11.
Breast cancer has traditionally been viewed as immunogenically 'cold,' but two immune checkpoint inhibitors have been approved in combination with chemotherapy for PD-L1 positive advanced triple-negative breast cancer (TNBC), and pembrolizumab was also recently approved for early stage TNBC. As the landscape is rapidly evolving, a comprehensive review of checkpoint inhibitors in breast cancer is needed to aid clinicians in selecting appropriate candidates for therapy, and to highlight ongoing promising studies in this area and topics in need of further investigation.
This review summarizes the latest evidence from completed and ongoing trials of immune checkpoint inhibitors. Ongoing studies were identified using a search of ClinicalTrials.gov with the term 'breast cancer' along with specific checkpoint inhibitor agents.
A number of novel combination strategies are under investigation to enhance response and overcome resistance to immunotherapy, with promising preliminary data from checkpoint inhibitors targeting TIGIT, combinations with small molecule inhibitors such as lenvatinib, and injectable agents directly influencing the immune microenvironment. As immunotherapy enters into the curative setting, biomarkers predictive of immunotherapy benefit are needed, as PD-L1 status has not been a helpful discriminator in completed trials in early-stage breast cancer.
乳腺癌传统上被认为是免疫原性“冷”肿瘤,但已有两种免疫检查点抑制剂与化疗联合用于 PD-L1 阳性晚期三阴性乳腺癌(TNBC),且帕博利珠单抗最近也被批准用于早期 TNBC。随着该领域的快速发展,需要对乳腺癌中的检查点抑制剂进行全面审查,以帮助临床医生为治疗选择合适的候选者,并强调该领域正在进行的有前途的研究和需要进一步研究的课题。
本综述总结了免疫检查点抑制剂在已完成和正在进行的临床试验中的最新证据。使用 ClinicalTrials.gov 进行了一项检索,使用了“乳腺癌”一词以及特定的检查点抑制剂药物,以确定正在进行的研究。
目前正在研究许多新的联合策略,以增强对免疫疗法的反应并克服耐药性,针对 TIGIT 的检查点抑制剂、与仑伐替尼等小分子抑制剂的联合以及直接影响免疫微环境的可注射药物的初步数据令人鼓舞。随着免疫疗法进入治疗环境,需要预测免疫疗法获益的生物标志物,因为 PD-L1 状态在早期乳腺癌的已完成试验中并不是一个有用的区分因素。