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Biomarker may inform de-escalation of chemotherapy for HER2-positive breast cancer
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Combining HER2-enriched and ERBB2 mRNA subtypes into one assay identified breast tumors with a high response to HER2-targeted therapy, according to a meta-analysis published in Journal of the National Cancer Institute.
These findings could lead to a de-escalation of chemotherapy by 40% for patients with HER2-positive breast cancer, according to the researchers.
“HER2-enriched subtype is a consistent biomarker of pathologic response following lapatinib and trastuzumab, and both HER2-enriched and ERBB2 mRNA levels provide additional information from each other, and their combination into a single variable is better,” Aleix Prat, MD, PhD, associate professor at University of Barcelona, and colleagues wrote. “To our knowledge, this is the first study to report that a combined score based on two different mRNA-based variables tracking the HER2 signaling pathway can identify high anti-HER2 sensitivity.”
Prat and colleagues analyzed 422 patients with HER2-positive tumors from five phase 2 and phase 3 trials (early disease, n = 305; advanced disease, n = 117). All patients were treated with neoadjuvant lapatinib (Tykerb, Novartis) or pertuzumab (Perjeta, Genentech) in combination with trastuzumab (Herceptin, Genentech) for 12 to 24 weeks.
In early disease, HER2-enriched subtype represented 83.8% of ERBB2-high and 44.7% of ERBB2-low tumors.
Pathologic complete response served as the primary endpoint. PFS, OS and overall response rate served as secondary endpoints.
After treatment with lapatinib and trastuzumab, a complete response occurred in 44.5% (95% CI, 35.4-53.9) of patients in the HER2-enriched and ERBB2-high group compared with 11.6% (95% CI, 6.9-18) of patients in the HER2-enriched and ERBB2-low group (adjusted OR = 6.05; 95% CI, 3.1-11.8).
Researchers observed similar findings with neoadjuvant trastuzumab and pertuzumab, with complete responses occurring in 66.7% (95% CI, 22.3-95.7) of the HER2-enriched and ERBB2-high group compared with 14.7% of the HER2-enriched and ERBB2-low group (adjusted OR = 11.6; 95% CI, 1.66-81.1).
In women with advanced disease, the HER2-enriched and ERBB2-high group was independently associated with higher ORR compared with the HER2-enriched and ERBB2-low group (16.3% vs. 3.7%), longer PFS (HR = 0.52; 95% CI, 0.35-0.79) and longer OS (HR = 0.66; 95% CI, 0.44-0.97).
Researchers noted that clinical groups used in this study were enrolled based on their respective studies, not for this specific one.
“Our study establishes the potential clinical validity of the HER2-enriched subtype and ERBB2 mRNA levels to predict anti-HER2 sensitivity,” Prat and colleagues wrote. “Our findings should now be externally validated, and research groups from the National Clinical Trial Network in the United States are now actively discussing the adoption of standardized and analytically validated assays to allow the prospective testing of this approach as an enrichment strategy for the primary endpoint in prospective trials for early-stage HER2-positive disease.” – by John DeRosier
Disclosures: Prat reports receiving consultant fees from Nanostring Technologies. Please see the study for all other authors’ relevant financial disclosures.
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