编者按：2024年欧洲肿瘤内科学会（ESMO）大会（9月13~17日，巴塞罗那）上展示的DESTINY-Gastric03研究（摘要号14010）评估了T-DXd联合FP和抗PD-1一线治疗食管、胃或胃食管结合部腺癌（GEJA）的疗效和安全性。在会议现场，我们特邀主要研究者、美国纪念斯隆凯特琳癌症中心的Yelena Janjigian教授在现场接受了我们的专访。

研究概况

背景

方法

结果

表1. 疗效和安全性总结

结论

研究者说

很高兴参加2024年ESMO年会。我们在大会上介绍了DESTINY-Gastric03研究。该研究是一项全球研究，纳入了包括欧洲、美国和世界其他地区（包括亚洲）的患者，旨在探索T-DXd（trastuzumab deruxtecan）联合卡培他滨或帕博利珠单抗一线治疗HER2阳性胃腺癌患者的疗效和安全性。

这项研究对于将抗体药物偶联物引入胃癌的一线治疗非常重要。我们知道T-DXd已作为曲妥珠单抗失败后常规使用的二、三线治疗。为了将T-DXd提到一线治疗，我们需要证明其与卡培他滨联合的安全性和可行性。令人兴奋的是，结果表明， T-DXd/卡培他滨组合一线治疗HER2阳性胃癌患者的无进展生存期为20个月。

与KEYNOTE-811研究类似，双重免疫检查点阻断与抗HER2疗法的结合很重要。在该研究中，我们还探讨了T-DXd、卡培他滨与帕博利珠单抗的组合，结果显示该方案似乎毒性太大，全剂量的三联组合不够理想。鉴于此，我们正在探索较低剂量的T-DXd（5.4 mg/kg）联合帕博利珠单抗和卡培他滨750 mg/m2的效果。我们的研究表明三联方案是可行的，总体缓解率令人满意，目前我们正在等待更新的生存数据。

总之，DESTINY-Gastric03研究了T-DXd单药治疗和T-DXd联合疗法的疗效与安全性，目前看来T-DXd三联方案是可行的。旨在探索T-DXd 5.4 mg/kg与卡培他滨和帕博利珠单抗或其他免疫检查点抑制剂联合治疗PD-L1（CPS≥1）和HER2阳性患者的Ⅲ期研究也正在进行中。

滑动查看英文原文：

Dr Janjigian: It is exciting to be at the ESMO 2024 Congress. We presented the DESTINY-Gastric03 study, which is exploring T-DXd (trastuzumab deruxtecan) monotherapy in combination with capecitabine or pembrolizumab in first-line patients with HER2-positive gastric adenocarcinoma. This study was important to be able to bring antibody drug conjugates to the first-line setting. Of course, you know T-DXd is standardly used after trastuzumab failure in the second- and third-line settings. To bring it to first-line, we needed to demonstrate safety and feasibility with capecitabine, and we did that. Excitedly, it was shown that for the combination of T-DXd/capecitabine in the first-line setting, progression-free survival was 20 months. This was a global study including patients in Europe, the United States, and the rest of the world including Asia. We also looked at the combination with pembrolizumab. As KEYNOTE-811 taught us, a combination of dual immune checkpoint blockade with anti-HER2 therapies is important, so we studied the combination of pembrolizumab and T-DXd and capecitabine, and it appeared to be too toxic. The triplet combination with full doses was insufficient, so we are now exploring the lower dose of T-DXd at 5.4 mg/kg plus pembrolizumab and 750 mg/m2  of capecitabine. We know that the triplet regimen is feasible - we demonstrated that. The overall response rate looked favorable, and now we are waiting for updated survival data. In summary, DESTINY-Gastric03 looked at T-DXd monotherapy and the T-DXd combinations. It appears T-DXd in triplet combination is feasible. The phase III studies are exploring the combination of T-DXd 5.4 mg/kg with capecitabine and pembrolizumab or other immune checkpoint blockade for PD-L1 (CPS ≥1) and HER2-positive patients.