Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, UK.
Curr Opin Oncol. 2022 Jul 1;34(4):389-394. doi: 10.1097/CCO.0000000000000859.
Metastatic oesophagogastric cancers carry a prognosis of generally less than 2 years despite current treatment. There has been recent excitement in the field focused on immune checkpoint inhibition though anti-PD-1 antibodies. In this article, we review recent phase 3 clinical trials evaluating first line PD-L1 inhibition in metastatic HER-2-negative oesophagogastric cancers and discuss future questions and challenges in the field.
Prior studies have shown promise using PD-L1 inhibition as third and fourth line treatment but recent phase 3 clinical trials have shown clear benefit to overall survival as first line treatment. PD-L1 inhibition as monotherapy demonstrated earlier death rates but there are a subset of patients with a long-term durable benefit when compared with chemotherapy. PD-L1 inhibition when combined with chemotherapy showed benefit in overall survival and progression-free survival and is enhanced in subsets of patients with increased PD-L1 expression.
Although there are still open questions how best to assess PD-L1 status, these studies provide clear evidence for use of PD-L1 inhibition combined with cytotoxic chemotherapy as first-line treatment in metastatic or unresectable oesophagogastric cancers that express PD-L1. In addition, they lay the groundwork for future studies evaluating PD-1 inhibition in earlier stages of disease.
目的综述：转移性胃食管癌症的预后通常不到 2 年，尽管目前有治疗方法，但情况仍然不容乐观。最近，免疫检查点抑制剂，特别是抗 PD-1 抗体，在该领域引起了广泛关注。在本文中，我们回顾了最近评估抗 PD-L1 抗体作为一线治疗 HER-2 阴性转移性胃食管癌症的 3 期临床试验，并讨论了该领域未来的问题和挑战。
最近的发现：先前的研究表明，PD-L1 抑制作为三线或四线治疗具有一定的前景，但最近的 3 期临床试验显示，PD-L1 抑制作为一线治疗具有明确的总生存期获益。PD-L1 抑制剂单药治疗的死亡率更高，但与化疗相比，仍有一部分患者具有长期持久的获益。PD-L1 抑制剂联合化疗在总生存期和无进展生存期方面均有获益，并且在 PD-L1 表达增加的亚组患者中获益更为显著。
总结：尽管如何最佳评估 PD-L1 状态仍存在疑问，但这些研究为 PD-L1 抑制剂联合细胞毒性化疗作为转移性或不可切除的胃食管癌症的一线治疗提供了明确的证据，这些癌症表达 PD-L1。此外，它们为未来在疾病早期阶段评估 PD-1 抑制剂的研究奠定了基础。
