Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F16%3AN0000065" target="_blank" >RIV/00209805:_____/16:N0000065 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S1470204515005513" target="_blank" >http://www.sciencedirect.com/science/article/pii/S1470204515005513</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/S1470-2045(15)00551-3" target="_blank" >10.1016/S1470-2045(15)00551-3</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

Popis výsledku v původním jazyce

We aimed to investigate the efficacy and safety of 12 months of neratinib after trastuzumab-based adjuvant therapy in patients with early-stage HER2-positive breast cancer. We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 495 centres. Eligible women had stage 1-3 HER2-positive breast cancer and had completed neoadjuvant and adjuvant trastuzumab therapy up to 2 years before randomisation. Patients were randomly assigned (1:1) to receive oral neratinib 240 mg per day or matching placebo. The randomisation sequence was generated with permuted blocks stratified by hormone receptor status vs hormone receptor-negative nodal status (0, 1-3, or ≥4), and trastuzumab adjuvant regimen. The primary outcome was invasive DFS at 2 years after randomisation. We randomly assigned 2840 women to receive neratinib or placebo. At 2 year follow-up, 70 invasive disease-free survival (DFS) events had occurred in patients in the neratinib group vs 109 events in the placebo group (stratified hazard ratio 0·67, 95% CI 0·50-0·91; p=0·0091). The 2-year invasive DFS rate was 93·9% (95% CI 92·4-95·2) in the neratinib group and 91·6% (90·0-93·0) in the placebo group. The most common grade 3-4 adverse events in patients in the neratinib group were diarrhoea, vomiting and nausea. QT prolongation occurred in 49 patients given neratinib and 93 patients given placebo, and decreases in left ventricular ejection fraction (≥grade 2) in 19 and 15. We recorded serious adverse events in 103 patients in the neratinib group and 85 in the placebo group. Seven deaths (4 patients in the neratinib group and 3 in the placebo group) unrelated to disease progression occurred after study drug discontinuation. Neratinib for 12 months significantly improved 2-year invasive DFS when given after chemotherapy and trastuzumab-based adjuvant therapy to women with HER2-positive breast cancer.

Název v anglickém jazyce

Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

Popis výsledku anglicky

We aimed to investigate the efficacy and safety of 12 months of neratinib after trastuzumab-based adjuvant therapy in patients with early-stage HER2-positive breast cancer. We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 495 centres. Eligible women had stage 1-3 HER2-positive breast cancer and had completed neoadjuvant and adjuvant trastuzumab therapy up to 2 years before randomisation. Patients were randomly assigned (1:1) to receive oral neratinib 240 mg per day or matching placebo. The randomisation sequence was generated with permuted blocks stratified by hormone receptor status vs hormone receptor-negative nodal status (0, 1-3, or ≥4), and trastuzumab adjuvant regimen. The primary outcome was invasive DFS at 2 years after randomisation. We randomly assigned 2840 women to receive neratinib or placebo. At 2 year follow-up, 70 invasive disease-free survival (DFS) events had occurred in patients in the neratinib group vs 109 events in the placebo group (stratified hazard ratio 0·67, 95% CI 0·50-0·91; p=0·0091). The 2-year invasive DFS rate was 93·9% (95% CI 92·4-95·2) in the neratinib group and 91·6% (90·0-93·0) in the placebo group. The most common grade 3-4 adverse events in patients in the neratinib group were diarrhoea, vomiting and nausea. QT prolongation occurred in 49 patients given neratinib and 93 patients given placebo, and decreases in left ventricular ejection fraction (≥grade 2) in 19 and 15. We recorded serious adverse events in 103 patients in the neratinib group and 85 in the placebo group. Seven deaths (4 patients in the neratinib group and 3 in the placebo group) unrelated to disease progression occurred after study drug discontinuation. Neratinib for 12 months significantly improved 2-year invasive DFS when given after chemotherapy and trastuzumab-based adjuvant therapy to women with HER2-positive breast cancer.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FD - Onkologie a hematologie

OECD FORD obor

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Projekt

<a href="/cs/project/NT13794" target="_blank" >NT13794: Analýza chaperonového systému a indentifikace nových biomarkerů u gynekologických malignit</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

The Lancet Oncology

ISSN

1470-2045

e-ISSN

—

Svazek periodika

17

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

367-377

Kód UT WoS článku

000371234900049

EID výsledku v databázi Scopus

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