Abstract P1-13-03: Effects of neratinib after trastuzumab-based adjuvant therapy in hormone receptor-positive HER2+ early-stage breast cancer: Exploratory analyses from the phase III ExteNET trial

摘要: Background: The international, randomized, placebo-controlled phase III ExteNET trial showed that a 1-year course of neratinib after trastuzumab-based adjuvant therapy significantly improved 2-year invasive disease-free survival (iDFS) in patients with early-stage HER2+ breast cancer (BC) (hazard ratio 0.67; 95% CI 0.50–0.91; p=0.009) [Chan et al. Lancet Oncol 2016]. significant iDFS benefit was maintained median 5 years9 follow-up 0.73; 0.57-0.92; p=0.008) [Martin ESMO 2017]. At both time-points, marked evident hormone receptor (HR)+ tumors, whereas HR– disease, initial improvements diminished completing treatment. We report exploratory analyses from the done to better characterize effects HR+ subgroup. Methods: Patients BC were randomly assigned oral 240 mg/day or placebo for 1 year standard primary and therapy. Randomization stratified by HR status (locally assessed), nodal status, trastuzumab regimen. Adjuvant endocrine recommended disease. Data concerning disease recurrences collected prospectively during 1-2 post-randomization, medical records 3–5 post-randomization. Primary endpoint: iDFS. Secondary endpoints: DFS including ductal carcinoma situ (DFS-DCIS); time distant recurrence (TTDR); (DDFS); cumulative incidence central nervous system (CNS) recurrences; overall (OS). Hazard ratios (95% CI) estimated using Cox proportional-hazards models. cut-off: March 2017. Clinicaltrials.gov: NCT00878709. Results: 2840 randomized (neratinib, n=1420; placebo, n=1420); 1631 (57%) had tumors n=816; n=815). 93% 94% groups, respectively, receiving at baseline. Efficacy outcomes cohort 5.2 years are shown table. In subgroup cohort, hazard 0.49 centrally confirmed (n=951), 0.58 who completed prior ≤12 months before randomization (n=1334). CNS OS data not yet mature. Conclusions: Neratinib associated an absolute 4.4% HR+/HER2+ follow-up. HR/HER2 cross-talk may underpin notable effect when given combination Citation Format: Chia SKL, Martin M, Iwata H, Moy B, Lalani AS, Holmes FA, Mansi J, von Minckwitz G, Buyse Delaloge S, Ejlertsen Yao Murias Rosales A, Hellerstedt Cold Inoue K, Shen Z-Z, Galeano T, Barrios CH, Chan A. Effects receptor-positive cancer: Exploratory [abstract]. In: Proceedings 2017 San Antonio Breast Cancer Symposium; Dec 5-9; Antonio, TX. Philadelphia (PA): AACR; Res 2018;78(4 Suppl):Abstract nr P1-13-03.