Afatinib alone or afatinib plus vinorelbine vs 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 trail

RCT (n=121) found primary endpoint of patient benefit at 12 weeks was not significantly different between afatinib containing treatments (ACTs) and investigator's choice of treatments; however, adverse events were frequent and ACTs seemed to be less well tolerated.

The primary endpoint, assessed in the intention-to-treat population, was patient benefit at 12 weeks, defined by an absence of CNS or extra-CNS disease progression, no tumour-related worsening of neurological signs or symptoms, and no increase in corticosteroid dose. Based on these data, no further development of afatinib for HER2-positive breast cancer is currently planned.

 

According to a commentary, despite the negative result, this well designed study provides important lessons for drug development and clinical care. It notes that it is the first study to take a pragmatic approach by allowing investigators to choose the active control regimen. It adds that “this trial also draws attention to the growing importance of both CNS activity and tolerability as potential differentiators between investigational drugs in what has become a crowded space.”