Britten Karissa, Bardia Aditya, McAndrew Nicholas
Division of Hematology-Oncology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
Target Oncol. 2025 Jun 20. doi: 10.1007/s11523-025-01157-1.
The development of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment over the last decade, starting with the US Food and Drug Administration (FDA) approval of ipilimumab in 2011. Since that time, the FDA has approved nine additional ICIs, which now serve as frontline agents in lung, colorectal, head and neck, genitourinary, and skin cancers. ICIs have been practice-changing across many cancer subtypes, and their role in breast cancer (particularly in early-stage disease) is a topic of ongoing research. The only current FDA-approved ICI indication in early breast cancer is for the use of pembrolizumab in high-risk, triple-negative breast cancer in combination with chemotherapy, based on results from the KEYNOTE-522 trial. Although numerous trials have further investigated the use of ICIs in early-stage triple-negative breast cancer, survival outcomes have been inconsistent. Studies investigating the use of ICIs in early-stage estrogen receptor-positive and human epidermal growth factor receptor 2-positive breast cancer are even more limited, although available data (especially for estrogen receptor-positive disease) are promising. Numerous studies are ongoing, including critical investigations into biomarkers that may help determine which patients with breast cancer are most likely to benefit from the addition of immunotherapy. In this review, we discuss the history of ICI development, key trials investigating the use of ICIs in early-stage breast cancer, and future directions in the field.
在过去十年中,免疫检查点抑制剂(ICI)的发展彻底改变了癌症治疗方式,始于2011年美国食品药品监督管理局(FDA)批准伊匹木单抗。自那时起,FDA又批准了另外九种ICI,它们现在已成为肺癌、结直肠癌、头颈癌、泌尿生殖系统癌和皮肤癌的一线治疗药物。ICI在许多癌症亚型中都改变了治疗方式,其在乳腺癌(尤其是早期疾病)中的作用是一个正在研究的课题。目前FDA批准的早期乳腺癌ICI唯一适应症是基于KEYNOTE-522试验的结果,即派姆单抗用于高危三阴性乳腺癌并联合化疗。尽管众多试验进一步研究了ICI在早期三阴性乳腺癌中的应用,但生存结果并不一致。研究ICI在早期雌激素受体阳性和人表皮生长因子受体2阳性乳腺癌中应用的研究更为有限,尽管现有数据(尤其是雌激素受体阳性疾病的数据)很有前景。许多研究正在进行中,包括对生物标志物的关键研究,这些生物标志物可能有助于确定哪些乳腺癌患者最有可能从免疫治疗中获益。在这篇综述中,我们讨论了ICI的发展历程、研究ICI在早期乳腺癌中应用的关键试验以及该领域的未来方向。
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