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Certain Molecular Subtypes in HR+/HER2- Breast Cancer Better Candidates for Neoadjuvant Therapy
Data from the recent phase 2, I-SPY2 trial suggests that hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer with Mammaprint High2 (MP2) and BluePrint (BP) Basal signatures are more likely to respond to neoadjuvant therapy. Additionally, the study authors wrote “an immune signature can identify patients more likely to respond to pembrolizumab.”
The trial enrolled 987 patients, 379 (38%) of which had HR+/HER2- disease. Patients with HR+/HER2- disease were randomized to treatment with either control of paclitaxel (n = 94) or one of the following investigational agents as neoadjuvant HR+/HER2- disease breast cancer therapy: veliparib/carboplatin (n = 32), neratinib (n = 17), MK2206 (n = 28), AMG386 (n = 62), ganitumab (n = 58), ganetespib (n = 48), and pembrolizumab (n = 40). The primary endpoint was estimated pathologic complete response (pCR) rate. When the predicted pCR in any signature met 85% probability of success, the regimens graduated. The estimated pCR rates for the 7 investigational agents in HR+/HER2- disease subset included analysis by the following clinical/molecular features: BP Luminal vs Basal and Mammprint High1 (MP1) va MP2.
Of the 7 investigational agents in the HR+/HER2- disease subset, only pembrolizumab met the graduation criteria. Overall, the pCR rates were higher in patients with MP2 disease (30%), when compared to MP1 (11%). In all arms of treatment except MK2206, HR+/HER2- BP Basal patients were more likely to achieve pCR than BP Luminal.
Source:
Huppert LA, Rugo HS, Pusztai L, et al. Pathologic complete response (pCR) rates for HR+/HER2- breast cancer by molecular subtype in the I-SPY2 Trial. Abstract presented at: American Society of Clinical Oncology Annual Meeting; June 3-7, 2022. Chicago, IL.
