Jubashi Amane, Nakayama Izuma, Koganemaru Shigehiro, Sakamoto Naoya, Oda Shioto, Matsubara Yuki, Miyashita Yu, Sato Seiya, Ushiyama Shinpei, Kobayashi Akinori, Okazaki Ukyo, Okemoto Dai, Yamamoto Kazumasa, Mishima Saori, Kotani Daisuke, Kawazoe Akihito, Hashimoto Tadayoshi, Nakamura Yoshiaki, Kuboki Yasutoshi, Bando Hideaki, Kojima Takashi, Yoshino Takayuki, Miyaaki Hisamitsu, Nakao Kazuhiko, Shitara Kohei
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan.
Gastric Cancer. 2025 Jan;28(1):63-73. doi: 10.1007/s10120-024-01560-z. Epub 2024 Nov 2.
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.
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.
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.
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.
曲妥珠单抗德鲁替康（T-DXd）是一种靶向人表皮生长因子受体2（HER2）阳性胃癌或胃食管交界癌（GC/GEJC）的抗体偶联药物。尽管T-DXd有效，但具有显著毒性，包括间质性肺疾病（ILD）。本研究评估了T-DXd治疗GC/GEJC的疗效、安全性及预后因素。
在我们机构进行了一项回顾性观察研究，回顾截至2023年9月接受T-DXd治疗患者的病历。符合条件的患者患有不可切除的晚期或复发性GC/GEJC，HER2状态为免疫组化（IHC）3+或IHC 2+/原位杂交（ISH）阳性，且先前接受过含曲妥珠单抗方案的治疗。
在分析的101例患者中，77例患者初始T-DXd剂量为6.4mg/kg，24例患者为5.4mg/kg。客观缓解率为54.3%，无进展生存期（PFS）中位数为5.4个月，总生存期（OS）中位数为11.4个月。PFS和OS较短的显著预后因素包括东部肿瘤协作组（ECOG）体力状态评分≥1、存在原发灶和腹膜转移，但不包括初始T-DXd剂量。14.9%的患者发生了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。
GC/GEJC患者接受T-DXd治疗后的预后与多个因素相关。肿瘤负荷是T-DXd相关ILD的潜在危险因素。需要进一步研究以根据肿瘤负荷优化给药并提高治疗指数。
