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GELATO试验

原文发布日期：2023-04-10

英文摘要：

摘要翻译：

原文链接：

文章：

GELATO试验

the GELATO trial

原文发布日期：2023-04-10

英文摘要：

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–1 min–1) 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.

摘要翻译：

浸润性乳头状乳腺癌（ILC）是第二种最常见的乳腺癌亚型，但针对 ILC 的专门临床试验尚未开展。通过转化研究发现了一个免疫相关联的 ILC 子类，在小鼠 ILC 模型中，联合使用免疫通路抑制剂和铂类药物显示了协同作用。在 II 期 GELATO 试验（NCT03147040）中，接受转移性 ILC 治疗的患者每周使用顺铂诱导免疫反应 12 周，随后从第三周起使用 Atezolizumab（PD-L1 阻断剂，每四周一次），直至出现进展。研究中共有 23 名可评估患者中只有 4 位出现了部分缓解（占总病例的 17%）和 2 位保持稳定，总的临床应答率为 26%。从这 6 例受试者中，有 4 例为三阴性 ILC（TN-ILC）。在治疗过程中，我们观察到 CD8+ T 细胞浸润增加、免疫检查点表达增强以及枯竭性 T 细胞减少。基于此 GELATO 试验，我们表明针对 ILC 的专门临床试验是可行的，并且 Atezolizumab 配顺铂显示出有前途的抗肿瘤活性，特别是对 TN-ILC患者效果显著，为后续需要大量开展 ILC 专门临床试验提供了研究思路。