Identification of early breast cancer patient cohorts who may benefit from lapatinib therapy

• Published in: European journal of cancer (1990) 2016-03, Vol.56, p.85-92
• Main Authors: Strasser-Weippl, Kathrin, Horick, Nora, Smith, Ian E, O'Shaughnessy, Joyce, Ejlertsen, Bent, Boyle, Frances, Buzdar, Aman U, Fumoleau, Pierre, Gradishar, William, Martin, Miguel, Moy, Beverly, Piccart-Gebhart, Martine, Pritchard, Kathleen I, Lindquist, Deborah, Rappold, Erica, Finkelstein, Dianne M, Goss, Paul E
• Format: Article
• Language: English
• Subjects: Adjuvant; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Breast Neoplasms - drug therapy; Breast Neoplasms - enzymology; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Chemotherapy, Adjuvant; Disease-Free Survival; Early breast cancer; Female; Hematology, Oncology and Palliative Medicine; Hormone receptor; Humans; In Situ Hybridization, Fluorescence; Kaplan-Meier Estimate; Lapatinib; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Patient Selection; Precision Medicine; Proportional Hazards Models; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Quinazolines - adverse effects; Quinazolines - therapeutic use; Receptor, ErbB-2 - antagonists & inhibitors; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Signal Transduction - drug effects; Time Factors; Treatment Outcome
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2015.12.024

Abstract In resource-constrained environments many patients with human epidermal growth factor receptor 2 (HER2)+ early breast cancer are currently not offered adjuvant anti-HER2 therapy. For patients who might be able to receive the tyrosine kinase inhibitor (TKI) lapatinib (e.g. after patent expiration), it is important to identify subgroups of patients for whom anti-HER2 TKI therapy could be beneficial. To do this, we used data from 2489 patients with centrally confirmed HER2+ disease enrolled in the adjuvant Tykerb Evaluation After Chemotherapy (TEACH) trial, investigating the effect of lapatinib in patients with HER2+ early breast cancer not treated with trastuzumab. We performed subgroup analyses and number-needed-to-treat (NNT) calculations using patient and tumour associated predictors. Hormone receptor negative (HR−) patients on lapatinib had a significantly prolonged disease-free survival (DFS) compared to HR− patients on placebo (hazard ratio 0.64, P = 0.003). For patients with HR– disease, starting treatment with lapatinib ≤1 year from diagnosis improved DFS by 12.1% [2.1–22.1] at 2 years and 15.7% [4.1–27.2] at 5 years. Depending on lymph node status and time since diagnosis the NNT for recurrence (at 5 years) was between 5.9 (node positive patients