2018 ASCO Annual Meeting!
Session: Breast Cancer—Local/Regional/Adjuvant
Type: Poster Session
Time: Saturday June 2, 8:00 AM to 11:30 AM
Location: Hall A
Duration of extended adjuvant therapy with neratinib in early-stage HER2+ breast cancer after trastuzumab-based therapy: Exploratory analyses from the phase III ExteNET trial.
2018 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #16)
J Clin Oncol 36, 2018 (suppl; abstr 524)
Author(s): Michael Gnant, Hiroji Iwata, Anna Elizabeth Bashford, Robert Separovic, Adolfo Murias, Elena Vicente, Julie Ann Means-Powell, Ingrid A. Mayer, Francis Mark Senecal, Rina Hui, Richard H. De Boer, Joanne Chiu, Anne Armstrong, Amparo Ruiz, Richard Bryce, Yining Ye, Arlene Chan; Comprehensive Cancer Centre, Medical University of Vienna, Vienna, Austria; Aichi Cancer Center Hospital, Nagoya, Japan; Auckland Hosp, Auckland, New Zealand; University Hospital for Tumors, Zagreb, Croatia; Hospital Universitario Insular de Gran Canaria, Las Palmas, Spain; Vanderbilt-Ingram Cancer Center, Nashville, TN; Northwest Medical Specialties PLLC, Tacoma, WA; Westmead Hospital and the University of Sydney, Sydney, Australia; Royal Melbourne Hospital, Melbourne, Australia; Queen Mary Hospital, Hong Kong, Hong Kong; Christie Hospital Manchester; University of Manchester, Manchester, United Kingdom; Fundación Instituto Valenciano de Oncología, Valencia, Spain; Puma Biotechnology Inc., Los Angeles, CA; Breast Cancer Research Centre - WA & Curtin University, Perth, Australia
Background: The optimal duration of adjuvant therapy with targeted agents remains a question of ongoing relevance in oncology. ExteNET, an international, randomized, placebo-controlled phase III trial, showed that neratinib given for 12 months after trastuzumab-based 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. Lancet Oncol 2016; Martin et al. Lancet Oncol 2017]. We examined the influence of duration of neratinib therapy on efficacy in the ExteNET study. Methods: Patients with early-stage HER2+ breast cancer were randomly assigned to oral neratinib 240 mg/day or placebo for 12 months (or until disease recurrence) after standard primary therapy and trastuzumab-based (neo)adjuvant therapy. Patients who received neratinib for ≤3 or ≥11 months (the median duration of neratinib treatment) were each compared with the ITT placebo group. iDFS (primary endpoint) was analyzed using Kaplan-Meier methods and Cox proportional-hazards models adjusted for prognostic factors. Data cut-off: March 1, 2017. Clinicaltrials.gov: NCT00878709. Results: ITT population comprised 2840 patients (neratinib, n = 1420; placebo, n = 1420). Median treatment duration (ITT population) was 11.6 and 11.8 months in the neratinib and placebo groups, respectively. 391 patients received neratinib for ≤3 months. 872 patients received neratinib for ≥11 months or stopped treatment prior to 11 months due to recurrence. Results after a median of 5.2 years' follow-up are shown below. Conclusions: These exploratory data suggest that patients who remained on neratinib for ≥11 months derived clear benefits from therapy, whereas neratinib efficacy was considerably reduced in those who stopped treatment early (≤3 months).Clinical trial information: NCT00878709
|Duration of neratinib||N||5-year iDFS rate, %||HR (95% CI)|
|≤3 months||1811||88.4||87.7||0.90 (0.59-1.32)|
|≥11 months||2292a||91.0||87.7||0.67 (0.50-0.88)|
a14 patients stopped treatment before 11 months due to recurrence.
bAdjusted for stratification factors.
1. TAILORx: Phase III trial of chemoendocrine therapy versus endocrine therapy alone in hormone receptor-positive, HER2-negative, node-negative breast cancer and an intermediate prognosis 21-gene recurrence score.