- 作者：Marina Chiara Garassino ; Olga Martelli ; Massimo Broggini ; Gabriella Farina ; Silvio Veronese ; Eliana Rulli ; Filippo Bianchi ; Anna Bettini ; Flavia Longo ; Luca Moscetti ; Maurizio Tomirotti ; Mirko Marabese ; Monica Ganzinelli ; Calogero Lauricella ; Roberto Labianca ; Irene Floriani ; Giuseppe Giaccone ; Valter Torri ; Alberto Scanni ; Silvia Marsoni ; et al.
- 刊名：Lancet Oncology
- 出版年：2013
- 出版时间：September, 2013
- 年：2013
- 卷：14
- 期：10
- 页码：981-988
- 全文大小：279 K
Summary
Background
Erlotinib is registered for treatment of all patients with advanced non-small-cell lung cancer (NSCLC). However, its efficacy for treatment of patients whose tumours are EGFR wild-type¡ªwhich includes most patients¡ªis still contentious. We assessed the efficacy of erlotinib compared with a standard second-line chemotherapy in such patients.Methods
We did this randomised controlled trial in 52 Italian hospitals. We enrolled patients who had metastatic NSCLC, had had platinum-based chemotherapy, and had wild-type EGFR as assessed by direct sequencing. Patients were randomly assigned centrally (1:1) to receive either erlotinib orally 150 mg/day or docetaxel intravenously 75 mg/m2 every 21 days or 35 mg/m2 on days 1, 8, and 15, every 28 days. Randomisation was stratified by centre, stage, type of first-line chemotherapy, and performance status. Patients and investigators who gave treatments or assessed outcomes were not masked to treatment allocation, investigators who analysed results were. The primary endpoint was overall survival in the intention-to-treat population. The study is registered at , number .
Findings
We screened 702 patients, of whom we genotyped 540. 222 patients were enrolled (110 assigned to docetaxel vs 112 assigned to erlotinib). Median overall survival was 8¡¤2 months (95 % CI 5¡¤8-10¡¤9) with docetaxel versus 5¡¤4 months (4¡¤5-6¡¤8) with erlotinib (adjusted hazard ratio [HR] 0¡¤73, 95 % CI 0¡¤53-1¡¤00; p=0¡¤05). Progression-free survival was significantly better with docetaxel than with erlotinib: median progression-free survival was 2¡¤9 months (95 % CI 2¡¤4-3¡¤8) with docetaxel versus 2¡¤4 months (2¡¤1-2¡¤6) with erlotinib (adjusted HR 0¡¤71, 95 % CI 0¡¤53-0¡¤95; p=0¡¤02). The most common grade 3-4 toxic effects were: low absolute neutrophil count (21 [20 % ] of 104 in the docetaxel group vs none of 107 in the erlotinib group), skin toxic effects (none vs 15 [14 % ]), and asthenia (ten [10 % ] vs six [6 % ]).
Interpretation
Our results show that chemotherapy is more effective than erlotinib for second-line treatment for previously treated patients with NSCLC who have wild-type EGFR tumours.
Funding
Agenzia Italiana del Farmaco.