Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study

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• 作者：Prof Caicun Zhou MD^‡ ; ; ^a ; ^{caicunzhou@yahoo.com.cn"" rel=""nofollow} ; Prof Yi-Long Wu MD^‡ ; ; ^b ; Prof Gongyan Chen PhD^c ; Prof Jifeng Feng MD^d ; Prof Xiao-Qing Liu MD^e ; Prof Changli Wang MD^f ; Prof Shucai Zhang MD^g ; Prof Jie Wang MDⁱ ; Songwen Zhou MD^a ; Shengxiang Ren MD^a ; Prof Shun Lu PhD^j ; Prof Li Zhang MD^l ; Prof Chengping Hu PhD^m ; Prof Chunhong Hu MDⁿ ; Prof Yi Luo MD^o ; Prof Lei Chen MD^p ; Prof Ming Ye MD^k ; Prof Jianan Huang MD^q ; Prof Xiuyi Zhi MD^h ; Prof Yiping Zhang MD^r ; Prof Qingyu Xiu MD^s ; Prof Jun Ma MD^t ; Prof Li Zhang MD^u ; Prof Changxuan You MD^v
• 刊名：Lancet Oncology
• 出版年：2011
• 出版时间：August 2011
• 年：2011
• 卷：12
• 期：8
• 页码：735-742
• 全文大小：264 K

文摘

Summary

Background

Activating mutations in EGFR are important markers of response to tyrosine kinase inhibitor (TKI) therapy in non-small-cell lung cancer (NSCLC). The OPTIMAL study compared efficacy and tolerability of the TKI erlotinib versus standard chemotherapy in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC.

Methods

We undertook an open-label, randomised, phase 3 trial at 22 centres in China. Patients older than 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR (exon 19 deletion or exon 21 L858R point mutation) received either oral erlotinib (150 mg/day) until disease progression or unacceptable toxic effects, or up to four cycles of gemcitabine plus carboplatin. Patients were randomly assigned (1:1) with a minimisation procedure and were stratified according to EGFR mutation type, histological subtype (adenocarcinoma vs non-adenocarcinoma), and smoking status. The primary outcome was progression-free survival, analysed in patients with confirmed disease who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov, number NCT00874419, and has completed enrolment; patients are still in follow-up.

Findings

83 patients were randomly assigned to receive erlotinib and 82 to receive gemcitabine plus carboplatin; 82 in the erlotinib group and 72 in the chemotherapy group were included in analysis of the primary endpoint. Median progression-free survival was significantly longer in erlotinib-treated patients than in those on chemotherapy (13.1 [95 % CI 10.58–16.53] vs 4.6 [4.21–5.42] months; hazard ratio 0.16, 95 % CI 0.10–0.26; p<0.0001). Chemotherapy was associated with more grade 3 or 4 toxic effects than was erlotinib (including neutropenia in 30 [42 % ] of 72 patients and thrombocytopenia in 29 [40 % ] patients on chemotherapy vs no patients with either event on erlotinib); the most common grade 3 or 4 toxic effects with erlotinib were increased alanine aminotransferase concentrations (three [4 % ] of 83 patients) and skin rash (two [2 % ] patients). Chemotherapy was also associated with increased treatment-related serious adverse events (ten [14 % ] of 72 patients [decreased platelet count, n=8; decreased neutrophil count, n=1; hepatic dysfunction, n=1] vs two [2 % ] of 83 patients [both hepatic dysfunction]).

Interpretation

Compared with standard chemotherapy, erlotinib conferred a significant progression-free survival benefit in patients with advanced EGFR mutation-positive NSCLC and was associated with more favourable tolerability. These findings suggest that erlotinib is important for first-line treatment of patients with advanced EGFR mutation-positive NSCLC.

Funding

F Hoffmann-La Roche Ltd (China); Science and Technology Commission of Shanghai Municipality.