Timing of initiation of neratinib after trastuzumab-based adjuvant therapy in early-stage HER2+ hormone receptor (HR)-negative breast cancer: Exploratory analyses from the phase III ExteNET trial.
Bildiriler > Özet Bildiri
Yazarlar: Bent Ejlertsen, Carlos H. Barrios, Erhan GÖKMEN, Nicholas Robert, Noelia Martinez, John S. Link, Serafin Morales, Manuel Ruiz Borrego, Manish Bhandari, Yoshiaki Rai, Adam Luczak, Takashi Fujita, Alvin Wong, Bin Yao, Miguel Martin
Journal of Clinical Oncology, , , Uluslararası, Özet Bildiri, Wos, cilt 36, ss 549-549
DOI: 10.1200/jco.2018.36.15_suppl.549
Özet
549 Background: ExteNET, an international, randomized, placebo-controlled phase III trial, showed that neratinib given for 1 year after trastuzumab-based adjuvant therapy significantly improved 2- (HR 0.67, p = 0.009) and 5-year (HR 0.73, p = 0.008) invasive disease-free survival (iDFS) in early-stage HER2+ breast cancer [Chan et al. 2016; Martin et al. 2017]. Prespecified subgroup analyses showed greater benefit with neratinib in HR+ than HR tumors, and in patients who initiated neratinib ≤12 months of completing trastuzumab. To better understand the effects of neratinib in patients with HR disease, we examined the impact on efficacy of the interval from prior trastuzumab to start of neratinib in the HR subpopulation. Methods: Patients with early-stage HER2+ breast cancer received oral neratinib 240 mg/day or placebo for 1 year after standard trastuzumab-based (neo)adjuvant therapy. iDFS, the primary study endpoint, was examined in subgroups categorized according to the interval between completing trastuzumab and randomization (i.e. 06, 612 and > 12 months). Data cut-off: March 1, 2017. Clinicaltrials.gov: NCT00878709. Results: The ITT population comprised 2840 patients; 1209 (43%) had HR disease (neratinib, n = 604; placebo, n = 605). Results after a median of 5.2 years in the HR subgroup are shown below. Conclusions: Patients with HER2+ HR tumors tend to recur early. The risk of recurrence is higher in patients who have recently completed trastuzumab-based therapy (reflected in the iDFS rates of the placebo group). Consistent with these observations, our analyses suggest that the benefits of neratinib in HR disease are greater when treatment is started closer to completion of trastuzumab (i.e. ≤6 months). Clinical trial information: NCT00878709.Interval between prior trastuzumab and randomization, months n 5-year iDFS rate, % Hazard ratio (95% CI)a Neratinib Placebo 06 695 88.9 86.1 0.73 (0.471.14) 612 268 86.1 91.7 1.61 (0.733.70) > 12 246 91.3 93.7 1.39 (0.523.90) Overall 1209 88.8 88.9 0.95 (0.661.35) aNeratinib vs placebo