Exploratory analysis of serum HER2 extracellular domain for HER2 positive gastric cancer treated with SOX plus trastuzumab

Takeru Wakatsuki; Naoki Ishizuka; Shuichi Hironaka; Keiko Minashi; Shigenori Kadowaki; Masahiro Goto; Hirokazu Shoji; Hidekazu Hirano; Izuma Nakayama; Hiroki Osumi; Mariko Ogura; Keisho Chin; Kensei Yamaguchi; Daisuke Takahari

doi:10.1007/s10147-024-02509-z

Exploratory analysis of serum HER2 extracellular domain for HER2 positive gastric cancer treated with SOX plus trastuzumab

Int J Clin Oncol. 2024 Apr 8. doi: 10.1007/s10147-024-02509-z. Online ahead of print.

Authors

Takeru Wakatsuki¹, Naoki Ishizuka², Shuichi Hironaka^{3

4}, Keiko Minashi³, Shigenori Kadowaki⁵, Masahiro Goto⁶, Hirokazu Shoji⁷, Hidekazu Hirano⁷, Izuma Nakayama⁸, Hiroki Osumi⁸, Mariko Ogura⁸, Keisho Chin⁸, Kensei Yamaguchi⁸, Daisuke Takahari⁸

Affiliations

¹ Department of Gastrointestinal Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan. takeru.wakatsuki@jfcr.or.jp.
² Department of Clinical Trial Planning, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
³ Clinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan.
⁴ Department of Medical Oncology, Faculty of Medicine, Kyorin University, Tokyo, Japan.
⁵ Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
⁶ Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University Hospital, Osaka, Japan.
⁷ Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁸ Department of Gastrointestinal Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan.

PMID: 38589679
DOI: 10.1007/s10147-024-02509-z

Abstract

Background: The aim of this study was to explore the clinical utility of serum HER2 extracellular domain (sHER2 ECD) using data from a clinical trial evaluating trastuzumab combined S-1 plus oxaliplatin (SOX) in HER2 positive gastric cancer.

Methods: sHER2 ECD were prospectively measured at baseline and subsequent treatment courses. Based on each quantile point of baseline sHER2 ECD levels and its early changes, patients were divided into two groups and compared clinical outcomes.

Results: 43 patients were enrolled, and 17 patients (39.5%) were positive for baseline sHER2 ECD. Higher baseline sHER2 ECD levels tended to have lower hazard ratios (HRs). When divided into two groups by baseline sHER2 ECD of 19.1 ng/ml, median progression-free survival (PFS) and overall survival (OS) was longer in the higher group (mPFS: 16.8 vs 8.7 months, p = 0.359. mOS: 35.5 vs 20.6 months, p = 0.270), respectively. After initiation of treatment, sHER2 ECD significantly decreased up until the third cycle. Higher reduction rates of sHER2 ECD within 3 cycles also tended to have lower HRs. When divided into two groups by reduction rate of 42.5%, mPFS and mOS was longer in the higher reduced group (mPFS: 17.2 vs 8.7 months, p = 0.095. mOS: 65.0 vs 17.8 months, p = 0.047), respectively. Furthermore, higher reduction rates could surrogate higher objective response rates (ORR) (ORR: 90% vs 63.2% for 29.5%, p = 0.065. 100% vs 70% for 42.5%, p = 0.085), respectively.

Conclusions: Baseline sHER2 ECD levels and its early decline may be useful biomarkers for SOX plus trastuzumab efficacy in HER2 positive gastric cancer.

Keywords: Biomarker; Gastric Cancer; HER2; Serum HER2 ECD; Trastuzumab.