Document Detail


Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial.
MedLine Citation:
PMID:  22285168     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer (NSCLC) with activating EGFR mutations. We aimed to assess the safety and efficacy of erlotinib compared with standard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC.
METHODS: We undertook the open-label, randomised phase 3 EURTAC trial at 42 hospitals in France, Italy, and Spain. Eligible participants were adults (> 18 years) with NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease (neoadjuvant or adjuvant chemotherapy ending ≥ 6 months before study entry was allowed). We randomly allocated participants (1:1) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of standard intravenous chemotherapy of cisplatin 75 mg/m(2) on day 1 plus docetaxel (75 mg/m(2) on day 1) or gemcitabine (1250 mg/m(2) on days 1 and 8). Carboplatin (AUC 6 with docetaxel 75 mg/m(2) or AUC 5 with gemcitabine 1000 mg/m(2)) was allowed in patients unable to have cisplatin. Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status (0 vs 1 vs 2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed safety in all patients who received study drug (≥ 1 dose). This study is registered with ClinicalTrials.gov, number NCT00446225.
FINDINGS: Between Feb 15, 2007, and Jan 4, 2011, 174 patients with EGFR mutations were enrolled. One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy. The preplanned interim analysis showed that the study met its primary endpoint; enrolment was halted, and full evaluation of the results was recommended. At data cutoff (Jan 26, 2011), median PFS was 9·7 months (95% CI 8·4-12·3) in the erlotinib group, compared with 5·2 months (4·5-5·8) in the standard chemotherapy group (hazard ratio 0·37, 95% CI 0·25-0·54; p < 0·0001). Main grade 3 or 4 toxicities were rash (11 [13%] of 84 patients given erlotinib vs none of 82 patients in the chemotherapy group), neutropenia (none vs 18 [22%]), anaemia (one [1%] vs three [4%]), and increased amino-transferase concentrations (two [2%] vs 0). Five (6%) patients on erlotinib had treatment-related severe adverse events compared with 16 patients (20%) on chemotherapy. One patient in the erlotinib group and two in the standard chemotherapy group died from treatment-related causes.
INTERPRETATION: Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors.
FUNDING: Spanish Lung Cancer Group, Roche Farma, Hoffmann-La Roche, and Red Temática de Investigacion Cooperativa en Cancer.
Authors:
Rafael Rosell; Enric Carcereny; Radj Gervais; Alain Vergnenegre; Bartomeu Massuti; Enriqueta Felip; Ramon Palmero; Ramon Garcia-Gomez; Cinta Pallares; Jose Miguel Sanchez; Rut Porta; Manuel Cobo; Pilar Garrido; Flavia Longo; Teresa Moran; Amelia Insa; Filippo De Marinis; Romain Corre; Isabel Bover; Alfonso Illiano; Eric Dansin; Javier de Castro; Michele Milella; Noemi Reguart; Giuseppe Altavilla; Ulpiano Jimenez; Mariano Provencio; Miguel Angel Moreno; Josefa Terrasa; Jose Muñoz-Langa; Javier Valdivia; Dolores Isla; Manuel Domine; Olivier Molinier; Julien Mazieres; Nathalie Baize; Rosario Garcia-Campelo; Gilles Robinet; Delvys Rodriguez-Abreu; Guillermo Lopez-Vivanco; Vittorio Gebbia; Lioba Ferrera-Delgado; Pierre Bombaron; Reyes Bernabe; Alessandra Bearz; Angel Artal; Enrico Cortesi; Christian Rolfo; Maria Sanchez-Ronco; Ana Drozdowskyj; Cristina Queralt; Itziar de Aguirre; Jose Luis Ramirez; Jose Javier Sanchez; Miguel Angel Molina; Miquel Taron; Luis Paz-Ares;
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Publication Detail:
Type:  Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2012-01-26
Journal Detail:
Title:  The Lancet. Oncology     Volume:  13     ISSN:  1474-5488     ISO Abbreviation:  Lancet Oncol.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-02     Completed Date:  2012-04-23     Revised Date:  2014-08-18    
Medline Journal Info:
Nlm Unique ID:  100957246     Medline TA:  Lancet Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  239-46     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00446225
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Aged
Antineoplastic Combined Chemotherapy Protocols / adverse effects,  therapeutic use*
Carboplatin / administration & dosage
Carcinoma, Non-Small-Cell Lung / drug therapy*,  enzymology,  genetics*,  mortality,  pathology
Chi-Square Distribution
Cisplatin / administration & dosage
Deoxycytidine / administration & dosage,  analogs & derivatives
Disease-Free Survival
Drug Administration Schedule
Europe
Exons
Female
Humans
Individualized Medicine
Kaplan-Meier Estimate
Lung Neoplasms / drug therapy*,  enzymology,  genetics*,  mortality,  pathology
Male
Middle Aged
Molecular Targeted Therapy
Mutation*
Patient Selection
Proportional Hazards Models
Prospective Studies
Protein Kinase Inhibitors / administration & dosage,  adverse effects,  therapeutic use*
Quinazolines / administration & dosage,  adverse effects,  therapeutic use*
Receptor, Epidermal Growth Factor / antagonists & inhibitors*,  genetics*
Taxoids / administration & dosage
Time Factors
Treatment Outcome
Chemical
Reg. No./Substance:
0/Protein Kinase Inhibitors; 0/Quinazolines; 0/Taxoids; 0W860991D6/Deoxycytidine; 15H5577CQD/docetaxel; B76N6SBZ8R/gemcitabine; BG3F62OND5/Carboplatin; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor; J4T82NDH7E/erlotinib; Q20Q21Q62J/Cisplatin
Comments/Corrections
Comment In:
Lancet Oncol. 2012 Mar;13(3):216-7   [PMID:  22285167 ]

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