PURPOSE Determination of optimal treatment strategies for HER2-positive advanced gastric cancer (AGC) in randomized trials is necessary despite difficulties in direct comparison between trastuzumab deruxtecan (T-DXd) and nivolumab as third or later-line treatments. MATERIALS AND METHODS This single-institution, retrospective study aimed to describe the real-world efficacy and safety of T-DXd and nivolumab as ≥ third line treatments for HER2-positive AGC between March 2016 and May 2022. Overall, 58 patients (median age, 64 years; 69% male) were eligible for the study (T-DXd group, n=20; nivolumab group, n=38). RESULTS Most patients exhibited a HER2 3+ status (72%) and presented metastatic disease at diagnosis (66%). The response rates of 41 patients with measurable lesions in the T-DXd and nivolumab groups were 50% and 15%, respectively. The T-DXd and nivolumab groups had a median progression-free survival of 4.8 months (95% confidence interval [CI], 3.3, 7.0) and 2.3 months (95% CI, 1.5, 3.5), median overall survival (OS) of 10.8 months (95% CI, 6.9, 23.8) and 11.7 months (95% CI, 7.6, 17.1), and grade 3 or greater adverse event rates of 50% and 2%, respectively. Overall, 64% patients received subsequent treatment. Among 23 patients who received both regimens, the T-DXd-nivolumab and nivolumab-T-DXd groups had a median OS of 14.0 months (95% CI, 5.0, not reached) and 19.3 months (95% CI, 9.5, 25.1), respectively. CONCLUSIONS T-DXd and nivolumab showed distinct efficacy and toxicity profiles as ≥ third line treatments for HER2-positive AGC. Considering the distinct features of each regimen, they may help clinicians personalize optimal treatment approaches for these patients.

中文翻译：

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Trastuzumab Deruxtecan 和 Nivolumab 作为 HER2 阳性晚期胃癌三线或后线治疗的疗效和安全性：单机构回顾性研究。

目的 尽管直接比较曲妥珠单抗 deruxtecan (T-DXd) 和纳武单抗作为第三线或后期治疗存在困难，但有必要在随机试验中确定 HER2 阳性晚期胃癌 (AGC) 的最佳治疗策略。材料和方法 这项单机构回顾性研究旨在描述 2016 年 3 月至 2022 年 5 月期间 T-DXd 和纳武单抗作为 HER2 阳性 AGC ≥ 三线治疗的实际疗效和安全性。总体而言，58 名患者（中位年龄） ，64 岁；69% 男性）符合研究资格（T-DXd 组，n=20；nivolumab 组，n=38）。结果 大多数患者表现出 HER2 3+ 状态 (72%)，并在诊断时出现转移性疾病 (66%)。T-DXd 组和纳武单抗组 41 名具有可测量病变的患者的缓解率分别为 50% 和 15%。T-DXd 和纳武单抗组的中位无进展生存期分别为 4.8 个月（95% 置信区间 [CI]，3.3，7.0）和 2.3 个月（95% CI，1.5，3.5），中位总生存期 (OS) 为10.8 个月（95% CI，6.9，23.8）和 11.7 个月（95% CI，7.6，17.1），3 级或以上不良事件发生率分别为 50% 和 2%。总体而言，64%的患者接受了后续治疗。在接受两种方案的 23 名患者中，T-DXd-nivolumab 和 nivolumab-T-DXd 组的中位 OS 分别为 14.0 个月（95% CI，5.0，未达到）和 19.3 个月（95% CI，9.5，25.1） ， 分别。结论 T-DXd 和纳武单抗作为 HER2 阳性 AGC 的≥三线治疗显示出不同的疗效和毒性特征。考虑到每种治疗方案的独特特征，它们可以帮助临床医生为这些患者制定个性化的最佳治疗方法。