This research article, recently published in our partner journal Future Oncology, evaluates the association of concordance between HER2 status and ERBB2 amplification with clinical benefit from 1L of trastuzumab for patients with advanced esophagogastric cancer (advEGC) treated in routine oncology practice. In addition, the authors examined the frequency of co-occurring genomic alterations associated with lack of trastuzumab benefit and explored associations between quantitative ERBB2 copy number alterations and clinical benefit for patients treated with trastuzumab. The study used the US-based de-identified Flatiron Health-Foundation Medicine EGC clinico-genomic database (FH-FMI CGDB) and 752 individuals with advEGC were selected for the analysis cohort. Overall HER2/ERBB2 concordance was 87.5% among HER2-tested patients with advEGC, which was driven by negative agreement. Patients with concordant (HER2+/ERBB2 amplification+) results had significantly longer time to treatment discontinuation and overall survival versus patients with discordant (HER2+/ERBB2 amplification-) results. Finally, the authors also observed that higher ERBB2 copy number may predict trastuzumab benefit. The findings from this study suggest that next-generation sequencing may have clinical value as a complement to traditional HER2 testing and warrant further investigation.
Purpose: To assess concordance between HER2 status measured by traditional methods and ERBB2 amplification measured by next-generation sequencing and its association with 1L trastuzumab clinical benefit in patients with advEGC.
Methods: Retrospective analysis of HER2/ERBB2 concordance using a de-identified US-based clinico-genomic database. Clinical outcomes were assessed for patients with HER2+ advEGC who received 1L trastuzumab.
Results: Overall HER2/ERBB2 concordance was 87.5%. Among patients who received 1L trastuzumab, concordant HER2/ERBB2 was associated with longer time-to-treatment discontinuation (TTD; aHR = 0.63 [95% CI: 0.43–0.90]) and overall survival (OS; aHR=0.51 [95% CI: 0.33–0.79]). ERBB2 CN≥25 (median) was associated with longer TTD (aHR=0.56 [95% CI: 0.35–0.88]) and OS (aHR=0.52 [95% CI: 0.30–0.91]).
Conclusion: HER2/ERBB2 concordance and higher ERBB2 CN predicted clinical benefit from trastuzumab.
Trastuzumab is a drug that has been shown to prolong survival in some patients with advanced esophagogastric cancer (advEGC) whose tumor expresses a protein biomarker called human epidermal growth factor receptor 2 (HER2). There are different methods for assessing whether a patient’s tumor expresses HER2, including but not limited to traditional methods such as immunohistochemistry (IHC) and in situ hybridization (ISH) and novel methods such as next-generation sequencing (NGS), which detects alterations in the gene (ERBB2) that encodes the HER2 protein. In our study, we assessed concordance between HER2 status (HER2 positive or HER2 negative) measured by traditional methods and ERBB2 amplification measured by NGS to determine whether there was an association between concordance and clinical benefit in patients with advEGC treated with trastuzumab. Our results suggest that, when HER2 positivity is detected through traditional methods, both ERBB2 concordance (i.e., agreement that a patient’s tumor had the biomarker) and a higher ERBB2 copy number (the amount of the ERBB2 gene that is expressed by the tumor) were associated with longer time-to-treatment discontinuation and overall survival in patients with advEGC treated with first-line trastuzumab.