Meeting: 2015 Breast Cancer Symposium
Title: Invasive disease-free survival benefit following neratinib as extended adjuvant therapy in centrally-confirmed HER2+ early-stage breast cancer: The ExteNET phase III randomized placebo-controlled trial.



Background: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor with clinical efficacy in trastuzumab pre-treated HER2-positive (HER2+) metastatic breast cancer (BC). ExteNET is an ongoing multicenter randomized placebo-controlled phase III trial evaluating the efficacy and safety of a 1-year course of neratinib in patients with early-stage HER2+ BC after trastuzumab-based adjuvant therapy (clinicaltrials.gov: NCT00878709). Methods: Women with locally-confirmed early-stage HER2+ BC were randomly assigned to oral neratinib 240mg/day or matching placebo for 1 year. Archived diagnostic tumor samples were submitted for HER2 gene amplification testing at a central laboratory. Primary endpoint: invasive disease-free survival (iDFS). Secondary endpoints: DFS including ductal carcinoma in situ (DFS+DCIS); distant disease-free survival (DDFS); time to distant recurrence (TDR). Stratified Cox proportional-hazards models were used to estimate hazard ratios (HR) for the ITT and amended ITT (aITT) populations; unstratified models were used for the centrally confirmed HER2 population. Treatment groups were compared using 2-sided log-rank tests. Results: The ITT population included 2840 patients (neratinib, N=1420; placebo, N=1420). The higher-risk aITT population (i.e. node-positive disease and randomized 1 year of completing prior trastuzumab) included 1873 patients (neratinib, N=938; placebo, N=935). Of the tumor samples analyzed, 1463 (86%) were centrally confirmed (neratinib, N=741; placebo, N=722). Conclusions: Neratinib significantly improves iDFS in trastuzumab-treated early-stage HER2+ BC patients. An enhanced treatment effect is observed with neratinib in women with centrally confirmed HER2+ tumors. Clinical trial information: NCT00878709PopulationHazard ratio [95% CI]iDFSDFS+DCISDDFSTDRITT (n=2840)0.67 [0.500.91]*0.63 [0.460.84]*0.75 [0.531.04]0.71 [0.501.00]aITT (n=1873)0.66 [0.470.92]*0.62 [0.440.86]*0.79 [0.541.15]0.77 [0.521.12]Centrally confirmed HER2+ (n=1463)0.52 [0.340.79]*0.50 [0.320.75]*0.47 [0.280.77]*0.47 [0.280.77]*p < 0.05