Predictive value of serum HER2 ECD in patients with HER2-positive advanced gastric cancer treated with trastuzumab plus chemotherapy

J Gastroenterol. 2015 Sep;50(9):955-61. doi: 10.1007/s00535-015-1046-3. Epub 2015 Feb 22.

Abstract

Background: The levels of serum HER2 extracellular domain (ECD) are highly correlated with tissue HER2 status in metastatic gastric cancer (AGC). We sought to explore whether serum HER2 ECD could predict the efficacy of trastuzumab-treated HER2-positive AGC.

Materials and methods: From 2011 to 2013, trastuzumab-treated AGC patients were enrolled. Serum HER2 ECD was centrally measured by chemiluminescence immunoassays (CLIA) method in available samples at baseline and after two cycles of trastuzumab combined with chemotherapy. The correlation between serum HER2 ECD and overall response rate (ORR) and progression-free survival (PFS) was analyzed.

Results: Sixty-five patients were analyzed with a median age of 58 years (range, 27-80 years). A significant difference of serum HER2 ECD levels was found between patients with HER2 IHC 3+ and those with HER2 IHC 2+ and FISH positive (p = 0.014). There was a significantly better ORR (80.00 vs. 50.00 %, p = 0.017) and PFS (median PFS, 268 vs. 139 days, p = 0.039) for patients with abnormal baseline serum HER2 ECD than for patients with normal serum HER2 ECD. Change in serum HER2 ECD during chemotherapy was significantly correlated with response to chemotherapy (79.17 vs. 51.52 %, p = 0.033) and PFS (median PFS, 303 vs. 147 days, p = 0.005) in patients with HER2-positive tumor tissue.

Conclusions: Our results support the clinical utility of measuring serum HER2 ECD levels in patients with advanced gastric cancer. Baseline and early changes in serum HER2 ECD could be useful for monitoring clinical outcome in HER2-positive AGC patients receiving trastuzumab-combined chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / blood*
  • Disease-Free Survival
  • Female
  • Humans
  • Luminescent Measurements
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Receptor, ErbB-2 / blood*
  • Stomach Neoplasms / blood*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Trastuzumab / therapeutic use*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab