A phase two randomised trial of neratinib monotherapy versus lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer

Miguel Martin, Jacques Bonneterre, Charles E. Geyer, Yoshinori Ito, Jungsil Ro, Istvan Lang, Sung Bae Kim, Caroline Germa, Jennifer Vermette, Kenneth Wang, Kongming Wang, Ahmad Awada

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Abstract

Background The safety and efficacy of neratinib monotherapy were compared with that of lapatinib plus capecitabine in patients with human epidermal growth factor receptor-2-positive (HER2+), locally advanced/metastatic breast cancer and prior trastuzumab treatment. Methods Patients received neratinib 240 mg/d continuously (n = 117) or lapatinib 1250 mg/d continuously plus capecitabine 2000 mg/m2 per day on days 1-14 of each 21-d cycle (n = 116). The primary aim was to demonstrate non-inferiority of neratinib for progression-free survival (PFS). Findings The non-inferiority of neratinib was not demonstrated when compared with lapatinib plus capecitabine (hazard ratio, 1.19; 95% confidence interval, 0.89-1.60; non-inferiority margin, 1.15). Median PFS for neratinib was 4.5 months versus 6.8 months for lapatinib plus capecitabine and median overall survival was 19.7 months versus 23.6 months. Objective response rate (neratinib, 29% versus lapatinib plus capecitabine, 41%; P = 0.067) and clinical benefit rate (44% versus 64%; P = 0.003) were lower for the neratinib arm but consistent with previously reported results. In both treatment arms, diarrhoea was the most frequently reported treatment-related adverse event of any grade (neratinib, 85% versus lapatinib plus capecitabine, 68%; P = 0.002) and of grade 3/4 (28% versus 10%; P < 0.001), but was typically managed with concomitant anti-diarrhoeal medication and/or study treatment modification. Importantly, neratinib had no significant skin toxicity. Interpretation The results are considered as inconclusive since neither inferiority nor non-inferiority of treatment with neratinib versus lapatinib plus capecitabine could be demonstrated. The study confirmed relevant single-agent clinical activity and acceptable overall tolerability of neratinib in patients with recurrent HER2+ advanced breast cancer.

Original languageEnglish
Pages (from-to)3763-3772
Number of pages10
JournalEuropean Journal of Cancer
Volume49
Issue number18
DOIs
Publication statusPublished - Dec 1 2013

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Keywords

  • Breast
  • phase II

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Martin, M., Bonneterre, J., Geyer, C. E., Ito, Y., Ro, J., Lang, I., Kim, S. B., Germa, C., Vermette, J., Wang, K., Wang, K., & Awada, A. (2013). A phase two randomised trial of neratinib monotherapy versus lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer. European Journal of Cancer, 49(18), 3763-3772. https://doi.org/10.1016/j.ejca.2013.07.142