Phase II trial of neratinib for HER2 mutated, non-amplified metastatic breast cancer (HER2mut MBC).

516Background: HER2 mutation occurs in ~2% of breast cancer (BC). Preclinical models suggested neratinib, an irreversible HER2/EGFR tyrosine kinase inhibitor, could be an effective treatment. This trial was conducted to assess the clinical benefit rate (CBR), defined as complete response (CR), partial response (PR) or stable disease (SD) ≥ 6 months (mo.), for neratinib in patients (pts) with HER2mutMBC (NCT01670877). Methods: This single arm phase II trial employed the Simon’s Optimal 2-stage design (1st stage: n=10, 2nd stage: n=19) to detect CBR of 20% versus the null hypothesis of 5% (80% power, 1-sided alpha 0.05). The primary endpoint is met if ≥ 4 CB is observed. Eligibility required the presence of somatic HER2mut and absent HER2 amplification. Activating HER2mut by in vitro study was required in the 2nd stage. Pts received neratinib 240 mg PO daily (28-day cycle) with prophylactic loperamide. Response was assessed every 2 cycles by RECIST 1.1. Enrollment was stopped early due to a protocol amendme...