Cancer Res Treat.  2024 Jan;56(1):199-207. 10.4143/crt.2023.490.

GASTric Cancer HER2 Re-Assessment Study 2 (GASTHER2): HER2 Re-assessment for Initially HER2-Negative Advanced Gastric Cancer Patients after Progression on First-Line Treatment

• Hyung J
• Kim HD
• Ryu MH
• Park YS
• Moon M
• Kang YK

• KMID: 2550336
• DOI: http://doi.org/10.4143/crt.2023.490

Abstract

Purpose
Heterogeneous human epidermal growth factor receptor 2 (HER2) overexpression in gastric cancer may lead to a misdiagnosis of HER2 status. Accurate assessment of HER2 status is essential for optimal treatment as novel HER2-directed agents are being investigated in various clinical settings. We evaluated the usefulness of HER2 re-assessment following progression on first-line treatment in initially HER2-negative advanced gastric cancer (AGC) patients.
Materials and Methods
We enrolled 177 patients with baseline HER2-negative AGC and performed HER2 re-assessment after progression on first-line treatment from February 2012 to June 2016 at Asan Medical Center, Seoul, Korea. The re-assessed HER2 status was analyzed with baseline HER2 status and clinical characteristics.
Results
The median age was 54 years (range, 24 to 80 years), and 123 patients (69.5%) were men. Seven patients (4.0%) were HER2-positive on the re-assessment. Patients with baseline HER2 negativity confirmed by a single test (n=100) had a higher HER2-positive re-assessment rate compared to those who had repeated baseline testing (n=77) (5.0% vs. 2.6%). Among the patients with single baseline HER2 testing, the rate was higher in patients with baseline HER2 immunohistochemistry (IHC) 1+ compared to those with IHC 0 (13.4% vs. 3.6%).
Conclusion
Overall, 4.0% of patients with baseline HER2-negative AGC were HER2-positive on re-assessment, and the HER2-positive re-assessment rate was higher among patients who had a single test at baseline. HER2 re assessment may be considered for initially HER2-negative patients to determine their eligibility for HER2-directed therapy, particularly if their HER2 negativity was determined by a single test, especially if they had a single baseline HER2 IHC 1+ test.

Keyword

Stomach neoplasms; HER2 re-assessment; HER2 heterogeneity; HER2-directed therapy

Figure

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  Fig. 1 Study outline. AGC, advanced gastric cancer; HER2, human epidermal growth factor receptor 2.

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  Fig. 2 Human epidermal growth factor receptor 2 (HER2) immunohistochemistry staining results at baseline and after progression on first-line treatment, and the response to second-line treatment with T-DM1. (A) Baseline HER2 immunohistochemistry of a resected gastric adenocarcinoma specimen showing no staining (×100). (B) HER2 immunohistochemistry of a biopsy specimen from an abdominal wall metastasis after progression on first-line treatment showing an intensity of 3+ (×100). (C) Representative abdominopelvic computed tomography scan showing a decrease in the diameter of the abdominal wall metastasis from 25.43 mm at baseline (left) to 8.88 mm (right) after two cycles of T-DM1.

Reference

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