Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial

被引:269
作者
Wu, Yi-Long [1 ]
Lee, Jin Soo [15 ]
Thongprasert, Sumitra [25 ]
Yu, Chong-Jen [19 ]
Zhang, Li [6 ]
Ladrera, Guia [17 ]
Srimuninnimit, Vichien [26 ]
Sriuranpong, Virote [27 ]
Sandoval-Tan, Jennifer [16 ]
Zhu, Yunzhong [2 ]
Liao, Meilin [3 ]
Zhou, Caicun [4 ]
Pan, Hongming [5 ]
Lee, Victor [10 ]
Chen, Yuh-Min [20 ,21 ]
Sun, Yan [9 ]
Margono, Benjamin [13 ]
Fuerte, Fatima [18 ]
Chang, Gee-Chen [22 ,23 ]
Seetalarom, Kasan [28 ]
Wang, Jie [7 ]
Cheng, Ashley [11 ]
Syahruddin, Elisna [12 ]
Qian, Xiaoping [8 ]
Ho, James [10 ]
Kurnianda, Johan [14 ]
Liu, Hsingjin Eugene [24 ]
Jin, Kate [30 ]
Truman, Matt [30 ]
Bara, Ilze [31 ]
Mok, Tony [29 ]
机构
[1] Guangdong Acad Med Sci, Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China
[2] Beijing Chest Hosp, Beijing, Peoples R China
[3] Shanghai Chest Hosp, Shanghai Lung Tumour Clin Med Ctr, Shanghai, Peoples R China
[4] Shanghai Pulm Hosp, Shanghai, Peoples R China
[5] Sir Run Run Shaw Hosp, Hangzhou, Zhejiang, Peoples R China
[6] Sun Yat Sen Univ, Ctr Canc, Guangzhou 510275, Guangdong, Peoples R China
[7] Beijing Canc Hosp, Beijing, Peoples R China
[8] Nanjing Gulou Hosp, Nanjing, Jiangsu, Peoples R China
[9] Chinese Acad Med Sci, Beijing 100730, Peoples R China
[10] Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China
[11] Princess Margaret Hosp, Hong Kong, Hong Kong, Peoples R China
[12] Persahabatan Hosp, Jakarta, Indonesia
[13] Dokter Soetomo Hosp, Surabaya, Indonesia
[14] Dr Sardjito Hosp, Yogyakarta, Indonesia
[15] Natl Canc Ctr, Goyang, South Korea
[16] Philippine Gen Hosp, Manila, Philippines
[17] Lung Ctr Philippines, Quezon City, Philippines
[18] Rizal Med Ctr, Pasig, Philippines
[19] Natl Taiwan Univ Hosp, Taipei, Taiwan
[20] Natl Yang Ming Med Univ, Sch Med, Taipei Vet Gen Hosp, Taipei, Taiwan
[21] Taipei Med Univ, Taipei, Taiwan
[22] Natl Yang Ming Univ, Fac Med, Sch Med, Taipei 112, Taiwan
[23] Taichung Vet Gen Hosp, Dept Internal Med, Div Chest Med, Taichung, Taiwan
[24] Taipei Med Univ, Wang Fang Hosp, Taipei, Taiwan
[25] Maharaj Nakorn Chiang Mai Hosp, Chiang Mai, Thailand
[26] Siriraj Hosp, Bangkok, Thailand
[27] Chulalongkorn Hosp, Bangkok, Thailand
[28] Phramongkutklao Hosp, Bangkok, Thailand
[29] Chinese Univ Hong Kong, Hong Kong Canc Inst, State Key Lab South China, Hong Kong, Hong Kong, Peoples R China
[30] Roche Prod Pty, Sydney, NSW, Australia
[31] F Hoffmann La Roche, Basel, Switzerland
关键词
1ST-LINE TREATMENT; OPEN-LABEL; PHASE-III; CARBOPLATIN-PACLITAXEL; MULTICENTER; GEFITINIB; THERAPY; HETEROGENEITY; GEMCITABINE; MUTATIONS;
D O I
10.1016/S1470-2045(13)70254-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background The results of FASTACT, a randomised, placebo-controlled, phase 2 study, showed that intercalated chemotherapy and erlotinib significantly prolonged progression-free survival (PFS) in patients with advanced non-small-cell lung cancer. We undertook FASTACT-2, a phase 3 study in a similar patient population. Methods In this phase 3 trial, patients with untreated stage IIIB/IV non-small-cell lung cancer were randomly assigned in a 1: 1 ratio by use of an interactive internet response system with minimisation algorithm (stratified by disease stage, tumour histology, smoking status, and chemotherapy regimen) to receive six cycles of gemcitabine (1250 mg/m(2) on days 1 and 8, intravenously) plus platinum (carboplatin 5 x area under the curve or cisplatin 75 mg/m(2) on day 1, intravenously) with intercalated erlotinib (150 mg/day on days 15-28, orally; chemotherapy plus erlotinib) or placebo orally (chemotherapy plus placebo) every 4 weeks. With the exception of an independent group responsible for monitoring data and safety monitoring board, everyone outside the interactive internet response system company was masked to treatment allocation. Patients continued to receive erlotinib or placebo until progression or unacceptable toxicity or death, and all patients in the placebo group were offered second-line erlotinib at the time of progression. The primary endpoint was PFS in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00883779. Findings From April 29, 2009, to Sept 9, 2010, 451 patients were randomly assigned to chemotherapy plus erlotinib (n=226) or chemotherapy plus placebo (n=225). PFS was significantly prolonged with chemotherapy plus erlotinib versus chemotherapy plus placebo (median PFS 7.6 months [95% CI 7.2-8.3], vs 6.0 months [5.6-7.1], hazard ratio [HR] 0.57 [0.47-0.69]; p<0.0001). Median overall survival for patients in the chemotherapy plus erlotinib and chemotherapy plus placebo groups was 18.3 months (16.3-20.8) and 15.2 months (12.7-17.5), respectively (HR 0.79 [0.64-0.99]; p=0.0420). Treatment benefit was noted only in patients with an activating EGFR gene mutation (median PFS 16.8 months [12.9-20.4] vs 6.9 months [5.3-7.6], HR 0.25 [0.16-0.39]; p<0.0001; median overall survival 31.4 months [22.2-undefined], vs 20.6 months [14.2-26.9], HR 0.48 [0.27-0.84]; p=0.0092). Serious adverse events were reported by 76 (34%) of 222 patients in the chemotherapy plus placebo group and 69 (31%) of 226 in the chemotherapy plus erlotinib group. The most common grade 3 or greater adverse events were neutropenia (65 [29%] patients and 55 [25%], respectively), thrombocytopenia (32 [14%] and 31 [14%], respectively), and anaemia (26 [12%] and 21 [9%], respectively). Interpretation Intercalated chemotherapy and erlotinib is a viable first-line option for patients with non-small-cell lung cancer with EGFR mutation-positive disease or selected patients with unknown EGFR mutation status.
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页码:777 / 786
页数:10
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