Prognostic and predictive factors for the efficacy and safety of trastuzumab deruxtecan in HER2-positive gastric or gastroesophageal junction cancer.

IF 6 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastric Cancer Pub Date : 2024-11-02 DOI:10.1007/s10120-024-01560-z

Amane Jubashi, Izuma Nakayama, Shigehiro Koganemaru, Naoya Sakamoto, Shioto Oda, Yuki Matsubara, Yu Miyashita, Seiya Sato, Shinpei Ushiyama, Akinori Kobayashi, Ukyo Okazaki, Dai Okemoto, Kazumasa Yamamoto, Saori Mishima, Daisuke Kotani, Akihito Kawazoe, Tadayoshi Hashimoto, Yoshiaki Nakamura, Yasutoshi Kuboki, Hideaki Bando, Takashi Kojima, Takayuki Yoshino, Hisamitsu Miyaaki, Kazuhiko Nakao, Kohei Shitara

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引用次数: 0

Abstract

Background: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate targeting HER2-positive gastric cancer or gastroesophageal junction cancer (GC/GEJC). Although effective, T-DXd has notable toxicities, including interstitial lung disease (ILD). This study evaluated the efficacy, safety, and prognostic factors associated with T-DXd for GC/GEJC.

Methods: A retrospective observational study was conducted at our institution by reviewing medical records of patients treated with T-DXd until September 2023. Eligible patients had unresectable advanced or recurrent GC/GEJC, HER2 status of IHC 3 + or IHC 2 + /ISH-positive, and prior treatment with trastuzumab-containing regimen.

Results: Among the 101 patients analyzed, the initial T-DXd dose was 6.4 mg/kg in 77 patients and 5.4 mg/kg in 24 patients. The objective response rate was 54.3%, with a median PFS of 5.4 months and a median OS of 11.4 months. The significant prognostic factors for shorter PFS and OS included ECOG PS ≥ 1, presence of primary lesion, and peritoneal metastasis but not the initial T-DXd dose. ILD occurred in 14.9% of patients. Notably, higher T-DXd dose and smaller tumor burden were associated with a higher incidence of ILD.

Conclusions: Several factors were associated with prognosis after T-DXd treatment in patients with GC/GEJC. Tumor burden is a potential risk factor for T-DXd-related ILD. Further studies are needed to optimize dosing based on tumor burden and to improve the therapeutic index.

查看原文本刊更多论文

HER2 阳性胃癌或胃食管交界处癌中曲妥珠单抗德鲁司坦疗效和安全性的预后和预测因素。

背景：曲妥珠单抗德鲁司坦（T-DXd）是一种针对HER2阳性胃癌或胃食管交界癌（GC/GEJC）的抗体药物共轭物。T-DXd虽然有效，但有明显的毒性，包括间质性肺病（ILD）。本研究评估了T-DXd治疗GC/GEJC的疗效、安全性和相关预后因素：我院通过查阅截至 2023 年 9 月接受 T-DXd 治疗的患者病历，开展了一项回顾性观察研究。符合条件的患者均为不可切除的晚期或复发性 GC/GEJC，HER2 状态为 IHC 3 + 或 IHC 2 + /ISH 阳性，且之前接受过含曲妥珠单抗方案的治疗：在分析的101名患者中，77名患者的初始T-DXd剂量为6.4 mg/kg，24名患者的初始T-DXd剂量为5.4 mg/kg。客观反应率为54.3%，中位PFS为5.4个月，中位OS为11.4个月。缩短PFS和OS的重要预后因素包括ECOG PS≥1、存在原发病灶和腹膜转移，但与初始T-DXd剂量无关。14.9%的患者出现了 ILD。值得注意的是，较高的T-DXd剂量和较小的肿瘤负荷与较高的ILD发生率相关：结论：有几个因素与GC/GEJC患者T-DXd治疗后的预后有关。肿瘤负荷是 T-DXd 相关 ILD 的潜在风险因素。需要进一步研究，根据肿瘤负荷优化剂量，提高治疗指数。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gastric Cancer 医学-胃肠肝病学

CiteScore

14.70

自引率

2.70%

发文量

审稿时长

6-12 weeks

期刊介绍： Gastric Cancer is an esteemed global forum that focuses on various aspects of gastric cancer research, treatment, and biology worldwide. The journal promotes a diverse range of content, including original articles, case reports, short communications, and technical notes. It also welcomes Letters to the Editor discussing published articles or sharing viewpoints on gastric cancer topics. Review articles are predominantly sought after by the Editor, ensuring comprehensive coverage of the field. With a dedicated and knowledgeable editorial team, the journal is committed to providing exceptional support and ensuring high levels of author satisfaction. In fact, over 90% of published authors have expressed their intent to publish again in our esteemed journal.