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Effect of Additional Trastuzumab in Neoadjuvant and Adjuvant Treatment for Patients with Resectable HER2-Positive Gastric Cancer

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Recent studies have reported a beneficial role of trastuzumab in neoadjuvant treatment (NAT) among resectable gastric cancer (GC) patients; however, the effect of adjuvant treatment (AT) combined with trastuzumab is understudied. We performed a retrospective cohort study to compare chemotherapies with or without trastuzumab among human epidermal growth factor receptor 2-positive (HER2 +) locally advanced GC patients in the AT and NAT settings, respectively.

Methods

We enrolled 208 HER2 + resected GC patients who underwent perioperative/postoperative treatment in 2010–2019 in a single-centered hospital, including 135 AT patients and 73 NAT patients. We used inverse probability of treatment weighting (IPTW) to balance potential confounding factors between the treatment groups, and estimated the treatment effect of trastuzumab. Pathological and survival outcomes were evaluated.

Results

The number of trastuzumab-exposed patients in the AT and NAT cohorts was 31 (23.0%) and 34 (46.6%), respectively. After IPTW adjustment, AT combined with trastuzumab showed a better overall survival (OS) over chemotherapy alone (p = 0.023). In IPTW-adjusted NAT analysis, trastuzumab-exposed patients had an improvement in tumor pathological regression and downstaging, with lower tumor regression grade scores (p = 0.002), ypTNM stages (p < 0.001), ypN stages (p = 0.035), and ypT stages (p < 0.001). Loss of HER2 positivity following trastuzumab treatment was observed in NAT patients; however, we did not observe any significant effect of trastuzumab on OS (p = 0.126).

Conclusions

Given the improvement in tumor regression and downstaging among NAT patients, and the OS benefit in AT patients, trastuzumab could be considered a promising treatment for locally advanced HER2 + GC patients. In particular, re-evaluation of HER2 status should be considered following NAT combined with trastuzumab.

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Acknowledgements

The authors thank all of the patients, their families, and medical staff members, especially the radiologists, who participated in this study.

Funding

This study was supported by the Peking University Clinical Scientist Program (BMU2019LCKXJ011), San Ming Project of Shenzhen city, China (No. SZSM201612051), National Science Foundation for Young Scientists of China (81802735), and China Postdoctoral Science Foundation (2019M650399).

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Author notes

  1. Qifei He, Jiahui Chen, Kai Zhou, and Jin Chenggen contributed equally to this work.

Authors and Affiliations

  1. Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Haidian District, Beijing, China

    Qifei He MD, Jiahui Chen MM, Kai Zhou MB, Chenggen Jin MM, Anqiang Wang MD, Ke Ji MD, Xin Ji PhD, Ji Zhang MD, Xiaojiang Wu MD, Zhaode Bu MD & Jiafu Ji MD, PhD

  2. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Xia Li MSc

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  1. Qifei He MD
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Contributions

Conceptualization: QH, ZB, and JJ. Data collection and check: JC, CJ, and KZ. Methodology: QH, JC, and XL. Formal analysis and investigation: QH, KZ, AW, XJ, and KJ. Writing—original draft preparation: QH and XL. Writing—review and editing: XJ, JC, ZB, and JJ. Funding acquisition: QH, AW, and JJ. Resources: QH, JZ, and XW. Validation: JZ, and XW. Supervision: ZB and JJ.

Corresponding authors

Correspondence to Zhaode Bu MD or Jiafu Ji MD, PhD.

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Disclosure

Qifei He, Jiahui Chen, Kai Zhou, Chenggen Jin, Anqiang Wang, Ke Ji, Xin Ji, Ji Zhang, Xiaojiang Wu, Xia Li, Zhaode Bu, and Jiafu Ji report no potential conflicts of interest.

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He, Q., Chen, J., Zhou, K. et al. Effect of Additional Trastuzumab in Neoadjuvant and Adjuvant Treatment for Patients with Resectable HER2-Positive Gastric Cancer. Ann Surg Oncol 28, 4413–4422 (2021). https://doi.org/10.1245/s10434-020-09405-6

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