Journal of Gastric Cancer

The Korean Gastric Cancer Association (대한위암학회)
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Efficacy and Safety of Trastuzumab Deruxtecan and Nivolumab as Third- or Later-Line Treatment for HER2-Positive Advanced Gastric Cancer: A Single-Institution Retrospective Study

  • Keitaro Shimozaki (Department of Gastrointestinal Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research) ;
  • Izuma Nakayama (Department of Gastrointestinal Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research) ;
  • Daisuke Takahari (Department of Gastrointestinal Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research) ;
  • Kengo Nagashima (Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital) ;
  • Koichiro Yoshino (Department of Gastrointestinal Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research) ;
  • Koshiro Fukuda (Department of Gastrointestinal Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research) ;
  • Shota Fukuoka (Department of Gastrointestinal Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research) ;
  • Hiroki Osumi (Department of Gastrointestinal Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research) ;
  • Mariko Ogura (Department of Gastrointestinal Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research) ;
  • Takeru Wakatsuki (Department of Gastrointestinal Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research) ;
  • Akira Ooki (Department of Gastrointestinal Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research) ;
  • Eiji Shinozaki (Department of Gastrointestinal Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research) ;
  • Keisho Chin (Department of Gastrointestinal Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research) ;
  • Kensei Yamaguchi (Department of Gastrointestinal Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research)
  • Received : 2023.04.27
  • Accepted : 2023.10.19
  • Published : 2023.10.31
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Abstract

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.

Keywords

Acknowledgement

We are deeply indebted to all the patients who participated in this study and to their families.

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