Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10374019" target="_blank" >RIV/00216208:11130/17:10374019 - isvavai.cz</a>

Alternative codes found

RIV/00064203:_____/17:10374019 RIV/00209805:_____/17:00077859

Result on the web

<a href="https://doi.org/10.1016/S1470-2045(17)30717-9" target="_blank" >https://doi.org/10.1016/S1470-2045(17)30717-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/S1470-2045(17)30717-9" target="_blank" >10.1016/S1470-2045(17)30717-9</a>

Result language

angličtina

Original language name

Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

Original language description

Background ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings. Methods In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (&gt;= 20 years in Japan) with stage 1-3c (modified to stage 2-3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1-3 vs or &gt;= 4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants. Findings Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5.2 years (IQR 2.1-5.3), patients in the neratinib group had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163 events; stratified hazard ratio 0.73, 95% CI 0.57-0.92, p=0.0083). The 5-year invasive disease-free survival was 90.2% (95% CI 88.3-91.8) in the neratinib group and 87.7% (85.7-89.4) in the placebo group. Without diarrhoea prophylaxis, the most common grade 3-4 adverse events in the neratinib group, compared with the placebo group, were diarrhoea (561 [40%] grade 3 and one [&lt;1%] grade 4 with neratinib vs 23 [2%] grade 3 with placebo), vomiting (grade 3:47 [3%] vs five [&lt;1%]), and nausea (grade 3:26 [2%] vs two [&lt;1%]). Treatment-emergent serious adverse events occurred in 103 (7%) women in the neratinib group and 85 (6%) women in the placebo group. No evidence of increased risk of long-term toxicity or long-term adverse consequences of neratinib-associated diarrhoea were identified with neratinib compared with placebo. Interpretation At the 5-year follow-up, 1 year of extended adjuvant therapy with neratinib, administered after chemotherapy and trastuzumab, significantly reduced the proportion of clinically relevant breast cancer relapses-ie, those that might lead to death, such as distant and locoregional relapses outside the preserved breast-without increasing the risk of long-term toxicity. An analysis of overall survival is planned after 248 events.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

The Lancet: Oncology

ISSN

1470-2045

e-ISSN

—

Volume of the periodical

18

Issue of the periodical within the volume

12

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

1688-1700

UT code for WoS article

000417001900046

EID of the result in the Scopus database

2-s2.0-85035115011