In the Herceptin Adjuvant (HERA) trial, 24% of patients (pts) who received T for 1 year (y) had a disease recurrence at 11 y follow-up. The primary analysis of the ExteNET trial, performed after 2 y follow-up, showed that a 1-y course of neratinib after T-based adjuvant therapy significantly improved invasive disease-free survival (iDFS) vs placebo in early-stage HER2+ BC (HR 0.67; 95% CI 0.50–0.91; p = 0.0091) [Chan et al. Lancet Oncol 2016]. We now report updated 5-y efficacy findings.
ExteNET is an international, multicenter, randomized, double-blind, placebo-controlled phase III trial. Pts received oral neratinib 240 mg/d or placebo for 1 y. After 2 y, randomized pts were asked to re-consent to collection of data concerning disease recurrences and survival from medical records for a further 3 y. The preplanned 5-y analysis was by intention-to-treat (ITT). Non-consenting pts were censored at their last physical examination. Primary endpoint: iDFS. HR (95% CI) were estimated using Cox proportional-hazards models. Data cut-off: March 2017. Clinicaltrials.gov: NCT00878709.
ITT population comprised 2840 pts (neratinib, n = 1420; placebo, n = 1420); 53 pts died during the initial 2-y follow-up. Among 2787 available pts, 2117 (76%) re-consented to additional follow-up (neratinib, n = 1028; placebo, n = 1089). Updated results after a median follow-up of 5.2 y are shown below. Secondary efficacy endpoints were supportive of the primary analysis.Table:
|Estimated 5-y iDFS rate, %|
|n||Neratinib||Placebo||HR (95% CI)||P value|
|Centrally confirmed HER2+||1796||90.4||88.2||0.74 (0.55–1.00)||0.047|
|HR + b||1631||91.2||86.8||0.60 (0.43–0.83)||0.002|
|Completed T ≤ 1 y of randomization||2297||89.7||86.5||0.70 (0.54–0.90)||0.006|
HR, hormone receptor; aStratified analysis; bStratification factor.
1 y of neratinib after T-based adjuvant therapy significantly improves iDFS at 5 y in pts with early-stage HER2+ BC, with a long-term sustained effect. A protocol-specified subgroup analysis suggested greater benefit in HR+ pts. Overall survival data are not yet mature.
Clinical trial identification
Legal entity responsible for the study
Wyeth, Pfizer and Puma Biotechnology
B. Ejlertsen: Grants to institution from NanoString, Novartis, and Roche, outside the submitted work. Travel support for educational meetings from AstraZeneca and Celgene. S. Delaloge: Grants and personal fees from Roche and GSK. G. von Minckwitz: Research funding to the institution from Amgen, Roche, Novartis, Celgene, Teva, AstraZeneca, Myriad Genetics, AbbVie and Vifor Pharma. C. Barrios: Grants from Amgen, AstraZeneca, Boehringer, Novartis, Pfizer, Roche, Celgene, Sanofi, Lilly, Puma. Personal fees from GSK, Novartis, Pfizer, Roche, Eisai. M. Gnant: Grants from Sanofi-Aventis, Novartis, Roche, GSK, Pfizer, Smith Medical. Personal fees from Novartis, AstraZeneca, Accelsiors, Esai. S-B. Kim: Research funding to the institution from Novartis, Sanofi-Aventis, Kyowa-Kirin Inc, and Dongkook Pharma Co., Ltd. R.P. Bryce: Emplyee and stock options: Puma Biotechnology Inc. F. Xu: Emplyee: Puma Biotechnology Inc. M. Buyse: Emplyee and shareholder: IDDI. A. Chan: Personal fees for educational meetings from Pfizer, Amgen. All other authors have declared no conflicts of interest.