Neoadjuvant Dual HER2 Blockade in HER2-Enriched Early Breast Cancer
In the Spanish phase II PAMELA study reported in The Lancet Oncology, Llombart-Cussac et al found that the HER2-enriched subtype was associated with the highest likelihood of pathologic complete response after neoadjuvant trastuzumab (Herceptin) and lapatinib (Tykerb) without chemotherapy in early-stage HER2-positive breast cancer. The HER2-enriched subtype exhibits the highest activation of the epidermal growth factor receptor–HER2 pathway.
Study Details
In the trial, 151 women with previously untreated centrally confirmed HER2-positive stage I to IIIA invasive breast cancer regardless of hormone receptor status were enrolled from 19 sites in Spain between October 2013 and November 2015. Patients received lapatinib at 1,000 mg/d and trastuzumab at a loading dose of 8 mg/kg followed by 6 mg/kg every 3 weeks for 18 weeks; hormone receptor–positive patients were given letrozole at 2.5 mg/d if menopausal or tamoxifen at 20 mg/d if premenopausal. Surgery was performed at 1 to 3 weeks after the last dose of study treatment. The primary outcome measure was the ability of the HER2-enriched subtype to predict pathologic complete response at the time of surgery.
Response Rates
At baseline, 101 patients (67%) had the HER2-enriched subtype, followed by 22 (15%), 16 (11%), 9 (6%), and 3 (2%) with luminal A, luminal B, basal-like, and normal-like subtypes, respectively.
At the time of surgery, 46 of the 151 patients (30%) had a pathologic complete response, including 41 of 101 (41%) with HER2-enriched subtype vs 5 of 50 (10%) with non–HER2-enriched subtypes (odds ratio = 6.2, P = .0004).
The investigators concluded: “The HER2-enriched subtype can identify patients with HER2-positive breast cancer who are likely to benefit from dual HER2 blockade therapies.”
The study was funded by GlaxoSmithKline, Susan Komen Foundation, CERCA Programme-Generalitat de Catalunya, Banco BilbaoVizcaya Argentaria Foundation, Pas a Pas, and Breast Cancer Research Foundation.
Aleix Prat, MD, of the Hospital Clinic of Barcelona, August Pi i Sunyer Biomedical Research Institute, is the corresponding author of The Lancet Oncology article.
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