Afatinib plus vinorelbine is no more effective than trastuzumab plus vinorelbine in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing metastatic breast cancer who had progressed on 1 previous trastuzumab treatment, a study published in the journal The Lancet Oncology has shown.1
Because trastuzumab resistance remains a therapeutic challenge in metastatic breast cancer, researchers sought to determine whether broader inhibition of ErbB receptors with afatinib would improve clinical outcomes compared with HER2 inhibition alone following progression on trastuzumab treatment.
For the open-label, phase 3 LUX-Breast 1 trial, investigators enrolled 508 women patients with HER2-overexpressing metastatic breast cancer who had progressed on or following adjuvant trastuzumab or frontline treatment with trastuzumab for metastatic disease.
Participants were randomly assigned 2:1 to receive afatinib 40 mg orally daily plus vinorelbine 25 mg/m2 intravenously weekly or trastuzumab 2 mg/kg weekly (after a 4 mg/kg loading dose) intravenously plus vinorelbine.
Results showed that at a follow-up of 9.3 months, median progression-free survival was 5.5 months (95% CI, 5.4 – 5.6) with afatinib and 5.6 months (95% CI, 5.3 – 7.3) with trastuzumab (HR, 1.10; 95% CI, 0.86 – 1.41; P = .43).
The most frequently reported treatment-related grade 3 or higher adverse events in the afatinib group were neutropenia, leukopenia, and diarrhea.
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Recruitment for the trial was ultimately stopped early after an independent data monitoring committee determined that the afatinib group had an unfavorable benefit-risk assessment. Patients receiving afatinib and vinorelbine had to switch to the other arm, afatinib or vinorelbine monotherapy, or receive treatment outside of the study.
“Trastuzumab-based therapy remains the treatment of choice for patients with HER2-positive metastatic breast cancer who had progressed on trastuzumab,” the authors concluded.
- Harbeck N, Huang C-S, Hurvitz S, et al. Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial [published online ahead of print January 25, 2016]. Lancet Oncol. doi: 10.1016/S1470-2045(15)00540-9.