HER2DX Shows Correlation Between ERBB2 mRNA Levels and Survival in HER2+ Breast Cancer

Javier Cortés, MD, PhD

HER2DX, a specialized genomic test for HER2-positive breast cancer, showed a strong association between ERBB2 mRNA score and survival outcomes in tumor samples from patients with advanced HER2-positive breast cancer.¹

The assay was used to evaluate long-term survival outcomes in 214 tumor samples from patients with advanced HER2-positive disease who received docetaxel plus trastuzumab (Herceptin) and pertuzumab (Perjeta) in the phase 3 CLEOPATRA trial (NCT00567190). In this patient population, a strong association was noted for ERBB2 mRNA score with progression-free survival (PFS) and overall survival (OS).

At a median follow-up of 99.9 months for CLEOPATRA, patients in the docetaxel plus trastuzumab and pertuzumab arm had superior PFS and OS outcomes compared with those who received docetaxel plus trastuzumab. These findings supported the 2012 FDA approval of docetaxel plus trastuzumab and pertuzumab for the treatment of this patient population.

Detailed findings from this HER2DX study will be presented at an upcoming medical conference and submitted for publication, according to a news release.

“The results of HER2DX in the CLEOPATRA trial are remarkable and highlight the test’s strong value in selecting patients who are more likely to achieve disease control and extended survival outcomes with the existing HER2 standards of care,” Javier Cortés, MD, PhD, chief of the International Breast Cancer Center in Barcelona Spain, as well as the co-founder of MedSIR, stated in the news release. “HER2DX in this setting will help decide the type of anti-HER2 therapies and their sequence. Patients with a HER2DX ERBB2-low score require closer attention, as they may not respond as well and may need alternative therapeutic strategies to improve their outcomes.”

HER2DX is a standardized 27-gene expression test for use in patients with early-stage HER2-positive breast cancer. This prognostic and predictive assay integrates clinical data, such as nodal status and tumor size, with biological data to track immune response, luminal differentiation, tumor cell proliferation, and expression of the HER2 17q12-17q21 chromosomal amplicon, including the ERBB2 gene.

Previous studies of HER2DX in HER2-positive breast cancer have shown that HER2DX ERBB2 score is significantly associated with improved HER2-targeted treatment outcomes. For instance, in a correlative analysis of pre-treatment tumor samples from the phase 2 PerELISA trial (NCT02411344), HER2DX predicted responses to neoadjuvant letrozole plus trastuzumab and pertuzumab in patients with resectable, HER2-positive, hormone receptor–positive breast cancer.² Among patients with endocrine therapy–sensitive disease (n = 40), HER2DX pathologic complete response (pCR) score (P = .0008; area under ROC [AUC] = 0.803) and HER2DX ERBB2 mRNA score (P = .0003; AUC = 0.896) were significantly associated with pCR. The pCR rates among patients with low (n = 26), medium (n = 13), and high (n = 1) HER2DX pCR scores were 7.7%, 46.2%, and 100.0%, respectively (P < .004). The pCR rates among patients with low (n = 12), medium (n = 13), and high (n = 15) HER2DX ERBB2 scores were 0.0%, 7.7%, and 53.3%, respectively (P = .001).

Additionally, a real-world study evaluated the utility of the HER2DX assay to predict responses in pre-treatment tumor samples from 85 patients with treatment-naive, HER2-positive metastatic breast cancer who received docetaxel plus trastuzumab and pertuzumab between 2010 and 2024.³ At a median follow-up of 44.2 months (range, 0.72-162.5), HER2DX ERBB2 score was significantly associated with PFS and OS. In patients with ERBB2-high disease, the median PFS and OS were 28.6 months and not reached vs 12.5 months (HR, 0.45; 95% CI, 0.26-0.78; P = .005) and 29.8 months (HR, 0.23; 95% CI, 0.12-0.44; P < .001), respectively, in the ERBB2-low group. Furthermore, all patients who were free of disease progression at 5 years and alive at 8 years (n = 4) had ERBB2-high disease.

“[The latest] positive results for HER2DX are another significant step forward for our company. We look forward to working with health care payers and providers to make this test reimbursed and available worldwide for both early and metastatic settings,” Patricia Villagrasa, PhD, chief executive officer and co-founder of Reveal Genomics, concluded in the news release.¹

References

1. REVEAL GENOMICS announces positive top-line results for HER2DX in CLEOPATRA phase III trial. News release. Reveal Genomics. September 10, 2024. Accessed September 10, 2024. https://www.reveal-genomics.com/press-releases/reveal-genomics-r-announces-positive-top-line-results-for-her2dx-r-in-cleopatra-phase-iii-trial
2. Guarneri V, Bras-Maristany F, Dieci MV, et al. HER2DX genomic test in HER2-positive/hormone receptor-positive breast cancer treated with neoadjuvant trastuzumab and pertuzumab: a correlative analysis from the PerELISA trial. EBioMedicine. 2022;85:104320. doi:10.1016/j.ebiom.2022.104320
3. Bayona RS, Martínez-Sáez O, Romero DR, et al. HER2DX ERBB2 mRNA score in first-line metastatic HER2-positive (HER2+) breast cancer (BC): implications for treatment stratification. ESMO Open. 2024;9(suppl 4):103022.