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

详细信息	查看全文 | 推荐本文 |

• 作者：Dr Rafael Rosell ; MD^a ; ^b ; ^{rrosell@iconcologia.net} ; Enric Carcereny ; MD^a ; Radj Gervais ; MD^c ; Prof Alain Vergnenegre ; MD^d ; Bartomeu Massuti ; MD^e ; Enriqueta Felip ; MD^f ; Ramon Palmero ; MD^g ; Ramon Garcia-Gomez ; MD^h ; Cinta Pallares ; MDⁱ ; Jose Miguel Sanchez ; MD^j ; ^k ; Rut Porta ; MD^l ; Manuel Cobo ; MD^m ; Pilar Garrido ; MDⁿ ; Flavia Longo ; MD^o ; Teresa Moran ; MD^a ; Amelia Insa ; MD^p ; Filippo De Marinis ; MD^q ; Romain Corre ; MD^r ; Isabel Bover ; MD^s ; Alfonso Illiano ; MD^t ; Eric Dansin ; MD^u ; Javier de Castro ; MD^v ; Michele Milella ; MD^w ; Noemi Reguart ; MD^x ; Giuseppe Altavilla ; MD^y ; Ulpiano Jimenez ; MD^z ; Mariano Provencio ; MD^aa ; Miguel Angel Moreno ; MD^ab ; Josefa Terrasa ; MD^ac ; Jose Muñ ; oz-Langa ; MD^ad ; Javier Valdivia ; MD^ae ; Dolores Isla ; MD^af ; Manuel Domine ; MD^ag ; Olivier Molinier ; MD^ah ; Prof Julien Mazieres ; MD^ai ; Nathalie Baize ; MD^aj ; Rosario Garcia-Campelo ; MD^ak ; Gilles Robinet ; MD^al ; Delvys Rodriguez-Abreu ; MD^am ; Guillermo Lopez-Vivanco ; MD^an ; Vittorio Gebbia ; MD^ao ; Lioba Ferrera-Delgado ; MD^ap ; Pierre Bombaron ; MD^aq ; Reyes Bernabe ; MD^ar ; Alessandra Bearz ; MD^as ; Angel Artal ; MD^at ; Enrico Cortesi ; MD^au ; Christian Rolfo ; MD^av ; Maria Sanchez-Ronco ; PhD^aw ; Ana Drozdowskyj ; PhD^ax ; Cristina Queralt ; PhD^a ; Itziar de Aguirre ; PhD^a ; Jose Luis Ramirez ; PhD^a ; Prof Jose Javier Sanchez ; MD^ay ; Miguel Angel Molina ; PhD^b ; Miquel Taron ; PhD^a ; ^b ; Luis Paz-Ares ; MD^az ; on behalf of the Spanish Lung Cancer Group in collaboration with the Groupe Franç ; ais de Pneumo-Cancé ; rologie ; the Associazione Italiana Oncologia Toracica
• 刊名：Lancet Oncology
• 出版年：2012
• 期刊代码：184_14702045
• 类别：med
• 出版时间：March, 2012
• 卷：13
• 期：3
• 页码：239-246
• 文件大小：246 K

摘要

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

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 鈮? 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/m² on day 1 plus docetaxel (75 mg/m² on day 1) or gemcitabine (1250 mg/m² on days 1 and 8). Carboplatin (AUC 6 with docetaxel 75 mg/m² or AUC 5 with gemcitabine 1000 mg/m²) 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 (鈮? dose). This study is registered with , number .

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路7 months (95%CI 8路4-12路3) in the erlotinib group, compared with 5路2 months (4路5-5路8) in the standard chemotherapy group (hazard ratio 0路37, 95%CI 0路25-0路54; p<0路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 Tem谩tica de Investigacion Cooperativa en Cancer.