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

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2024年11月2日

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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

摘要

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.