Neoadjuvant Dual HER2 Blockade in HER2-Enriched Early Breast Cancer

Key Points

  • In patients with early-stage HER2-positive breast cancer, dual HER2 blockade produced the highest pathologic complete response rate in the HER2-enriched subtype.
  • Pathologic complete response was observed in 41% vs 10% of patients.

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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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