Shimozaki Keitaro, Nakayama Izuma, Takahari Daisuke, Nagashima Kengo, Yoshino Koichiro, Fukuda Koshiro, Fukuoka Shota, Osumi Hiroki, Ogura Mariko, Wakatsuki Takeru, Ooki Akira, Shinozaki Eiji, Chin Keisho, Yamaguchi Kensei
Department of Gastrointestinal Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
J Gastric Cancer. 2023 Oct;23(4):609-621. doi: 10.5230/jgc.2023.23.e41.
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.
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).
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.
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.
尽管在曲妥珠单抗德鲁替康（T-DXd）和纳武利尤单抗作为三线或更后线治疗的直接比较中存在困难，但在随机试验中确定HER2阳性晚期胃癌（AGC）的最佳治疗策略是必要的。
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和纳武利尤单抗作为HER2阳性AGC的≥三线治疗的真实世界疗效和安全性。总体而言，58例患者（中位年龄64岁；69%为男性）符合研究条件（T-DXd组，n = 20；纳武利尤单抗组，n = 38）。
大多数患者表现为HER2 3+状态（72%），诊断时出现转移性疾病（66%）。T-DXd组和纳武利尤单抗组中41例有可测量病灶患者的缓解率分别为50%和15%。T-DXd组和纳武利尤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）分别为10.8个月（95% CI，6.9，23.8）和11.7个月（95% CI，7.6，17.1），3级或更高等级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。在接受两种治疗方案的23例患者中，T-DXd-纳武利尤单抗组和纳武利尤单抗-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）。
T-DXd和纳武利尤单抗作为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点，它们可能有助于临床医生为这些患者制定个性化的最佳治疗方案。
