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NEW YORK (Reuters Health) – In more than one of five patients with metastatic gastric cancer (mGC), results of human epidermal growth factor receptor-2 (HER2) testing by local and central labs do not align, and this has implications for response to trastuzumab therapy, according to a study from Germany.

Trastuzumab is an anti-HER2-targeted therapy approved for first-line treatment of HER2+ mGC. The drug has been shown to improve survival in HER2-positive patients, but not all patients respond and most eventually progress.

Assessment of HER2 in gastric cancer is known to be challenging, note Dr. Florian Lordick at Leipzig University Medical Center and colleagues in the Journal of Clinical Oncology.

In the VARIANZ study, they investigated HER2 expression, HER2 test deviations and their impact on survival in a multicenter, injectable prednisone prospective study of patients being treated for mGC and followed for up to 48 months. A total of 548 patients were enrolled and 77 had HER2-positive mGC by central assessment (14.1%).

They found a “high deviation rate” of 22.7% between HER2 test results performed by two independent laboratories (central and local testing).

Patients who received trastuzumab for centrally confirmed HER2-positive mGC (HER2+ by both central and local testing) lived significantly longer than patients who received trastuzumab for local HER2-positive but central HER2-negative mGC (20.5 months vs. 10.9 months; hazard ratio, 0.42; P<0.001).

“Patients with equivocal HER2 test results show only intermediate HER2 expression, characterized by <40% of tumor cells staining positive for HER2. These patients did seemingly not benefit from the addition of trastuzumab to chemotherapy in our study as overall survival equals the survival of HER2-negative patients who were not treated with trastuzumab,” the authors report.

In the centrally confirmed cohort (central and local HER2+ results), significantly more tumor cells stained HER2-positive than in the unconfirmed cohort, and the HER2 amplification ratio was significantly higher, the authors note.

They determined that “optimized thresholds” for predicting benefit from trastuzumab are a minimum of 40% HER2-positive tumor cells and a HER2 amplification ratio of 3.0 or higher. “Borderline HER2 positivity and heterogeneity of HER2 expression should be considered as resistance factors for HER2-targeting treatment of mGC,” they conclude.

They also suggest that detailed reports with quantification of HER2 expression and amplification levels “may improve selection of patients for HER2-directed treatment.”

The study was supported by the German Federal Ministry for Education and Research. Author disclosures are available with the original article.

SOURCE: https://bit.ly/3wi4pmj Journal of Clinical Oncology, online March 25, 2021.

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