曲妥珠单抗联合 SOX 方案治疗 HER2 阳性胃癌患者血清 HER2 细胞外域的探索性分析。
Exploratory analysis of serum HER2 extracellular domain for HER2 positive gastric cancer treated with SOX plus trastuzumab.
机构信息
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.
Department of Clinical Trial Planning, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
出版信息
Int J Clin Oncol. 2024 Jun;29(6):801-812. doi: 10.1007/s10147-024-02509-z. Epub 2024 Apr 8.
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.
背景
本研究旨在通过一项评估曲妥珠单抗联合 S-1 加奥沙利铂（SOX）治疗人表皮生长因子受体 2（HER2）阳性胃癌的临床试验数据，探讨血清 HER2 细胞外结构域（sHER2 ECD）的临床应用价值。
方法
在基线和后续治疗过程中，前瞻性测量 sHER2 ECD。根据基线 sHER2 ECD 水平及其早期变化的每个分位数点，将患者分为两组，并比较临床结局。
结果
共纳入 43 例患者，其中 17 例（39.5%）基线 sHER2 ECD 阳性。较高的基线 sHER2 ECD 水平往往预示着较低的风险比（HR）。当根据基线 sHER2 ECD 水平分为 19.1ng/ml 时，较高组的中位无进展生存期（PFS）和总生存期（OS）较长（mPFS：16.8 比 8.7 个月，p=0.359.mOS：35.5 比 20.6 个月，p=0.270）。治疗开始后，sHER2 ECD 在第三个周期明显下降。在前三个周期内 sHER2 ECD 下降率较高的患者也往往预示着较低的 HR。当根据 42.5%的降低率分为两组时，较高降低组的 mPFS 和 mOS 较长（mPFS：17.2 比 8.7 个月，p=0.095.mOS：65.0 比 17.8 个月，p=0.047）。此外，较高的降低率可替代较高的客观缓解率（ORR）（ORR：29.5%时为 90%比 63.2%，p=0.065.42.5%时为 100%比 70%，p=0.085）。
结论
基线 sHER2 ECD 水平及其早期下降可能是 SOX 联合曲妥珠单抗治疗 HER2 阳性胃癌疗效的有用生物标志物。
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