There was no difference in benefit between afatinib-containing treatment and investigator’s choice of treatments in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and central nervous system (CNS) recurrence or progression, but afatinib-containing treatments appeared to be less well tolerated, a new study published online ahead of print in the journal The Lancet Oncology has shown.1

Because the brain metastases that progressed after brain radiotherapy and HER2-targeted systemic therapy are difficult to treat in patients with advanced HER2-positive breast cancer, researchers sought to evaluate the efficacy and safety of afatinib alone or in combination with vinorelbine, compared with treatment of investigator’s choice in women with brain metastases that have progressed during or after treatment with trastuzumab, lapatinib, or both.

For the open-label, multicenter, phase 2 trial, researchers enrolled 121 patients with HER2-overexpressing breast cancer and CNS recurrence or progression during or after treatment with trastuzumab, lapatinib, or both. 

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Participants were randomly assigned 1:1:1 to receive afatinib 40 mg orally daily, afatinib plus vinorelbine 25 mg/m2 intravenously weekly, or investigator’s choice of treatment for 3 cycles until disease progression, unacceptable toxicity, or patient withdrawal.

Results showed that patient benefit at 12 weeks was achieved in 30.0% (95% CI, 16.6 – 46.5) for those who received afatinib alone, 34.2% (95% CI, 19.6 – 51.4) for those who received afatinib plus vinorelbine, and 41.9% (95% CI, 27.0 – 57.9) for those given investigator’s choice; however, there was no significant difference between afatinib alone or afatinib plus vinorelbine and investigator’s choice.

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In regard to safety, grade 3 and 4 diarrhea and neutropenia were more frequent in the afatinib-containing treatments than treatments of investigator’s choice.

“No further development of afatinib for HER2-positive breast cancer is currently planned,” the authors noted.


  1. Cortés J, Dieras V, Ro R, et al. Afatinib alone or afatinib plus vinorelbine versus investigator’s choice of treatment for HER2-positive breast cancer with progressive brain metastases after trastuzumab, lapatinib, or both (LUX-Breast 3): a randomised, open-label, multicentre, phase 2 trial [published online ahead of print November 16, 2015]. Lancet Oncol. doi: 10.1016/S1470-2045(15)00373-3.