Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Department of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Nat Cancer. 2023 Apr;4(4):535-549. doi: 10.1038/s43018-023-00542-x. Epub 2023 Apr 10.
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.
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。
