Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): An open-label, randomised, phase 3 trial

The LUX-Breast 1 study group

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47 Citations (Scopus)

Abstract

Background: Trastuzumab resistance is a key therapeutic challenge in metastatic breast cancer. We postulated that broader inhibition of ErbB receptors with afatinib would improve clinical outcomes compared with HER2 inhibition alone in patients who had progressed on previous trastuzumab treatment. LUX-Breast 1 compared afatinib plus vinorelbine with trastuzumab plus vinorelbine for such patients with HER2-positive metastatic breast cancer. Methods: We did this open-label trial at 350 hospitals in 41 countries worldwide. We enrolled female patients with HER2-overexpressing metastatic breast cancer who had progressed on or following adjuvant trastuzumab or first-line treatment of metastatic disease with trastuzumab. Participants were randomly assigned (2:1) to receive oral afatinib (40 mg/day) plus intravenous vinorelbine (25 mg/m 2 per week) or intravenous trastuzumab (2 mg/kg per week after 4 mg/kg loading dose) plus vinorelbine. Randomisation was done centrally and stratified by previous trastuzumab treatment (adjuvant vs first-line treatment), hormone receptor status (oestrogen receptor and progesterone receptor positive vs others), and region. The primary endpoint was progression-free survival, assessed in the intention-to-treat population. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT01125566. Findings: Between Aug 26, 2010, and April 26, 2013, we enrolled 508 patients: 339 assigned to the afatinib group and 169 assigned to the trastuzumab group. Recruitment was stopped on April 26, 2013, after a benefit-risk assessment by the independent data monitoring committee was unfavourable for the afatinib group. Patients on afatinib plus vinorelbine had to switch to trastuzumab plus vinorelbine, afatinib monotherapy, vinorelbine monotherapy, or receive treatment outside of the trial. Median follow-up was 9·3 months (IQR 3·7-16·0). Median progression-free survival was 5·5 months (95% CI 5·4-5·6) in the afatinib group and 5·6 months (5·3-7·3) in the trastuzumab group (hazard ratio 1·10 95% CI 0·86-1·41; p=0·43). The most common drug-related adverse events of grade 3 or higher were neutropenia (190 [56%] of 337 patients in the afatinib group vs 102 [60%] of 169 patients in the trastuzumab group), leucopenia (64 [19%] vs 34 [20%]), and diarrhoea (60 [18%] vs none). Interpretation: Trastuzumab-based therapy remains the treatment of choice for patients with HER2-positive metastatic breast cancer who had progressed on trastuzumab. Funding: Boehringer Ingelheim.

Original languageEnglish
Pages (from-to)357-366
Number of pages10
JournalThe Lancet Oncology
Volume17
Issue number3
DOIs
Publication statusPublished - 2016 Mar 1

Fingerprint

Breast
Breast Neoplasms
Therapeutics
vinorelbine
Trastuzumab
BIBW 2992
Disease-Free Survival
Clinical Trials Data Monitoring Committees
Leukopenia
Progesterone Receptors
Random Allocation
Neutropenia
Drug-Related Side Effects and Adverse Reactions
Estrogen Receptors
Diarrhea
Hormones

ASJC Scopus subject areas

  • Oncology

Cite this

@article{7f445ba2851c4cbbb27ac29e66a444ca,
title = "Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): An open-label, randomised, phase 3 trial",
abstract = "Background: Trastuzumab resistance is a key therapeutic challenge in metastatic breast cancer. We postulated that broader inhibition of ErbB receptors with afatinib would improve clinical outcomes compared with HER2 inhibition alone in patients who had progressed on previous trastuzumab treatment. LUX-Breast 1 compared afatinib plus vinorelbine with trastuzumab plus vinorelbine for such patients with HER2-positive metastatic breast cancer. Methods: We did this open-label trial at 350 hospitals in 41 countries worldwide. We enrolled female patients with HER2-overexpressing metastatic breast cancer who had progressed on or following adjuvant trastuzumab or first-line treatment of metastatic disease with trastuzumab. Participants were randomly assigned (2:1) to receive oral afatinib (40 mg/day) plus intravenous vinorelbine (25 mg/m 2 per week) or intravenous trastuzumab (2 mg/kg per week after 4 mg/kg loading dose) plus vinorelbine. Randomisation was done centrally and stratified by previous trastuzumab treatment (adjuvant vs first-line treatment), hormone receptor status (oestrogen receptor and progesterone receptor positive vs others), and region. The primary endpoint was progression-free survival, assessed in the intention-to-treat population. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT01125566. Findings: Between Aug 26, 2010, and April 26, 2013, we enrolled 508 patients: 339 assigned to the afatinib group and 169 assigned to the trastuzumab group. Recruitment was stopped on April 26, 2013, after a benefit-risk assessment by the independent data monitoring committee was unfavourable for the afatinib group. Patients on afatinib plus vinorelbine had to switch to trastuzumab plus vinorelbine, afatinib monotherapy, vinorelbine monotherapy, or receive treatment outside of the trial. Median follow-up was 9·3 months (IQR 3·7-16·0). Median progression-free survival was 5·5 months (95{\%} CI 5·4-5·6) in the afatinib group and 5·6 months (5·3-7·3) in the trastuzumab group (hazard ratio 1·10 95{\%} CI 0·86-1·41; p=0·43). The most common drug-related adverse events of grade 3 or higher were neutropenia (190 [56{\%}] of 337 patients in the afatinib group vs 102 [60{\%}] of 169 patients in the trastuzumab group), leucopenia (64 [19{\%}] vs 34 [20{\%}]), and diarrhoea (60 [18{\%}] vs none). Interpretation: Trastuzumab-based therapy remains the treatment of choice for patients with HER2-positive metastatic breast cancer who had progressed on trastuzumab. Funding: Boehringer Ingelheim.",
author = "{The LUX-Breast 1 study group} and Nadia Harbeck and Huang, {Chiun Sheng} and Sara Hurvitz and Yeh, {Dah Cherng} and Zhimin Shao and Im, {Seock Ah} and Jung, {Kyung Hae} and Kunwei Shen and Jungsil Ro and Jacek Jassem and Qingyuan Zhang and Im, {Young Hyuck} and Marek Wojtukiewicz and Qiang Sun and Chen, {Shin Cheh} and Goeldner, {Rainer Georg} and Martina Uttenreuther-Fischer and Binghe Xu and Martine Piccart-Gebhart and Dmitriy Krasnozhon and Zhongsheng Tong and Arora, {Rajender Singh} and Jacob, {Linu Abraham} and Elzbieta Staroslawska and Xiaojia Wang and {Satya Suresh Attili}, V. and Mehta, {Ajay Omprakash} and Lee, {Soo Hyeon} and Tseng, {Ming Ling} and Perera, {N. A.Mahendra} and Manon Huizing and Bohuslav Melichar and Ruta Grigiene and Lavina Bharwani and Javier Cortes and Mirta Garcia and Jacquie Chirgwin and Yauheni Baranau and Nikolai Ermakov and Wei Li and Tongyu Lin and Shukui Qin and Peng Shen and Junlan Yang and Nadine Dohollou and Pierre Kerbrat and Christoph Uleer and Harmut Kristeleit and Nagarkar, {Rajanish V.} and Park, {Kyong Hwa}",
year = "2016",
month = "3",
day = "1",
doi = "10.1016/S1470-2045(15)00540-9",
language = "English",
volume = "17",
pages = "357--366",
journal = "The Lancet Oncology",
issn = "1470-2045",
publisher = "Lancet Publishing Group",
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TY - JOUR

T1 - Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1)

T2 - An open-label, randomised, phase 3 trial

AU - The LUX-Breast 1 study group

AU - Harbeck, Nadia

AU - Huang, Chiun Sheng

AU - Hurvitz, Sara

AU - Yeh, Dah Cherng

AU - Shao, Zhimin

AU - Im, Seock Ah

AU - Jung, Kyung Hae

AU - Shen, Kunwei

AU - Ro, Jungsil

AU - Jassem, Jacek

AU - Zhang, Qingyuan

AU - Im, Young Hyuck

AU - Wojtukiewicz, Marek

AU - Sun, Qiang

AU - Chen, Shin Cheh

AU - Goeldner, Rainer Georg

AU - Uttenreuther-Fischer, Martina

AU - Xu, Binghe

AU - Piccart-Gebhart, Martine

AU - Krasnozhon, Dmitriy

AU - Tong, Zhongsheng

AU - Arora, Rajender Singh

AU - Jacob, Linu Abraham

AU - Staroslawska, Elzbieta

AU - Wang, Xiaojia

AU - Satya Suresh Attili, V.

AU - Mehta, Ajay Omprakash

AU - Lee, Soo Hyeon

AU - Tseng, Ming Ling

AU - Perera, N. A.Mahendra

AU - Huizing, Manon

AU - Melichar, Bohuslav

AU - Grigiene, Ruta

AU - Bharwani, Lavina

AU - Cortes, Javier

AU - Garcia, Mirta

AU - Chirgwin, Jacquie

AU - Baranau, Yauheni

AU - Ermakov, Nikolai

AU - Li, Wei

AU - Lin, Tongyu

AU - Qin, Shukui

AU - Shen, Peng

AU - Yang, Junlan

AU - Dohollou, Nadine

AU - Kerbrat, Pierre

AU - Uleer, Christoph

AU - Kristeleit, Harmut

AU - Nagarkar, Rajanish V.

AU - Park, Kyong Hwa

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Background: Trastuzumab resistance is a key therapeutic challenge in metastatic breast cancer. We postulated that broader inhibition of ErbB receptors with afatinib would improve clinical outcomes compared with HER2 inhibition alone in patients who had progressed on previous trastuzumab treatment. LUX-Breast 1 compared afatinib plus vinorelbine with trastuzumab plus vinorelbine for such patients with HER2-positive metastatic breast cancer. Methods: We did this open-label trial at 350 hospitals in 41 countries worldwide. We enrolled female patients with HER2-overexpressing metastatic breast cancer who had progressed on or following adjuvant trastuzumab or first-line treatment of metastatic disease with trastuzumab. Participants were randomly assigned (2:1) to receive oral afatinib (40 mg/day) plus intravenous vinorelbine (25 mg/m 2 per week) or intravenous trastuzumab (2 mg/kg per week after 4 mg/kg loading dose) plus vinorelbine. Randomisation was done centrally and stratified by previous trastuzumab treatment (adjuvant vs first-line treatment), hormone receptor status (oestrogen receptor and progesterone receptor positive vs others), and region. The primary endpoint was progression-free survival, assessed in the intention-to-treat population. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT01125566. Findings: Between Aug 26, 2010, and April 26, 2013, we enrolled 508 patients: 339 assigned to the afatinib group and 169 assigned to the trastuzumab group. Recruitment was stopped on April 26, 2013, after a benefit-risk assessment by the independent data monitoring committee was unfavourable for the afatinib group. Patients on afatinib plus vinorelbine had to switch to trastuzumab plus vinorelbine, afatinib monotherapy, vinorelbine monotherapy, or receive treatment outside of the trial. Median follow-up was 9·3 months (IQR 3·7-16·0). Median progression-free survival was 5·5 months (95% CI 5·4-5·6) in the afatinib group and 5·6 months (5·3-7·3) in the trastuzumab group (hazard ratio 1·10 95% CI 0·86-1·41; p=0·43). The most common drug-related adverse events of grade 3 or higher were neutropenia (190 [56%] of 337 patients in the afatinib group vs 102 [60%] of 169 patients in the trastuzumab group), leucopenia (64 [19%] vs 34 [20%]), and diarrhoea (60 [18%] vs none). Interpretation: Trastuzumab-based therapy remains the treatment of choice for patients with HER2-positive metastatic breast cancer who had progressed on trastuzumab. Funding: Boehringer Ingelheim.

AB - Background: Trastuzumab resistance is a key therapeutic challenge in metastatic breast cancer. We postulated that broader inhibition of ErbB receptors with afatinib would improve clinical outcomes compared with HER2 inhibition alone in patients who had progressed on previous trastuzumab treatment. LUX-Breast 1 compared afatinib plus vinorelbine with trastuzumab plus vinorelbine for such patients with HER2-positive metastatic breast cancer. Methods: We did this open-label trial at 350 hospitals in 41 countries worldwide. We enrolled female patients with HER2-overexpressing metastatic breast cancer who had progressed on or following adjuvant trastuzumab or first-line treatment of metastatic disease with trastuzumab. Participants were randomly assigned (2:1) to receive oral afatinib (40 mg/day) plus intravenous vinorelbine (25 mg/m 2 per week) or intravenous trastuzumab (2 mg/kg per week after 4 mg/kg loading dose) plus vinorelbine. Randomisation was done centrally and stratified by previous trastuzumab treatment (adjuvant vs first-line treatment), hormone receptor status (oestrogen receptor and progesterone receptor positive vs others), and region. The primary endpoint was progression-free survival, assessed in the intention-to-treat population. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT01125566. Findings: Between Aug 26, 2010, and April 26, 2013, we enrolled 508 patients: 339 assigned to the afatinib group and 169 assigned to the trastuzumab group. Recruitment was stopped on April 26, 2013, after a benefit-risk assessment by the independent data monitoring committee was unfavourable for the afatinib group. Patients on afatinib plus vinorelbine had to switch to trastuzumab plus vinorelbine, afatinib monotherapy, vinorelbine monotherapy, or receive treatment outside of the trial. Median follow-up was 9·3 months (IQR 3·7-16·0). Median progression-free survival was 5·5 months (95% CI 5·4-5·6) in the afatinib group and 5·6 months (5·3-7·3) in the trastuzumab group (hazard ratio 1·10 95% CI 0·86-1·41; p=0·43). The most common drug-related adverse events of grade 3 or higher were neutropenia (190 [56%] of 337 patients in the afatinib group vs 102 [60%] of 169 patients in the trastuzumab group), leucopenia (64 [19%] vs 34 [20%]), and diarrhoea (60 [18%] vs none). Interpretation: Trastuzumab-based therapy remains the treatment of choice for patients with HER2-positive metastatic breast cancer who had progressed on trastuzumab. Funding: Boehringer Ingelheim.

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U2 - 10.1016/S1470-2045(15)00540-9

DO - 10.1016/S1470-2045(15)00540-9

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C2 - 26822398

AN - SCOPUS:84960496215

VL - 17

SP - 357

EP - 366

JO - The Lancet Oncology

JF - The Lancet Oncology

SN - 1470-2045

IS - 3

ER -