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PD-L1 阻断联合卡铂作为转移性乳腺 lobular 癌的免疫诱导治疗:GELATO 试验。

PD-L1 blockade in combination with carboplatin as immune induction in metastatic lobular breast cancer: the GELATO trial.

机构信息

Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.

Department of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.

出版信息

Nat Cancer. 2023 Apr;4(4):535-549. doi: 10.1038/s43018-023-00542-x. Epub 2023 Apr 10.

Abstract

Invasive lobular breast cancer (ILC) is the second most common histological breast cancer subtype, but ILC-specific trials are lacking. Translational research revealed an immune-related ILC subset, and in mouse ILC models, synergy between immune checkpoint blockade and platinum was observed. In the phase II GELATO trial ( NCT03147040 ), patients with metastatic ILC were treated with weekly carboplatin (area under the curve 1.5 mg ml min) as immune induction for 12 weeks and atezolizumab (PD-L1 blockade; triweekly) from the third week until progression. Four of 23 evaluable patients had a partial response (17%), and 2 had stable disease, resulting in a clinical benefit rate of 26%. From these six patients, four had triple-negative ILC (TN-ILC). We observed higher CD8 T cell infiltration, immune checkpoint expression and exhausted T cells after treatment. With this GELATO trial, we show that ILC-specific clinical trials are feasible and demonstrate promising antitumor activity of atezolizumab with carboplatin, particularly for TN-ILC, and provide insights for the design of highly needed ILC-specific trials.

摘要

浸润性小叶乳腺癌(ILC)是第二常见的组织学乳腺癌亚型,但缺乏专门针对 ILC 的试验。转化研究揭示了一个与免疫相关的 ILC 亚群,在小鼠 ILC 模型中,观察到免疫检查点阻断与铂类药物的协同作用。在 II 期 GELATO 试验(NCT03147040)中,转移性 ILC 患者接受每周卡铂(曲线下面积 1.5mg·ml·min)作为 12 周的免疫诱导治疗,并从第 3 周开始每 3 周接受 atezolizumab(PD-L1 阻断;每周三次)治疗,直至疾病进展。23 名可评估患者中有 4 名(17%)出现部分缓解,2 名患者疾病稳定,临床获益率为 26%。这 6 名患者中有 4 名患有三阴性 ILC(TN-ILC)。我们观察到治疗后 CD8 T 细胞浸润、免疫检查点表达和耗竭 T 细胞增加。通过这项 GELATO 试验,我们表明专门针对 ILC 的临床试验是可行的,并证明 atezolizumab 联合卡铂具有有前途的抗肿瘤活性,特别是对 TN-ILC,并为急需的 ILC 特异性试验设计提供了思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e6/10132987/2a6627a6538b/43018_2023_542_Fig1_HTML.jpg

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