Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study
机构：[1]Guangdong Lung Cancer Institute, Guangdong General Hospital, and Guangdong Academy of Medical Sciences, Guangzhou, China广东省人民医院[2]Fudan University Affiliated Zhongshan Hospital, Shanghai, China[3]Zhejiang Cancer Hospital, Hangzhou, China浙江省肿瘤医院[4]Hunan Cancer Hospital, Changsha, China[5]The Affiliated Hospital of Medical College Qingdao University, Qingdao, China[6]Liaoning Cancer Hospital, Shenyang, China[7]Fujian Medical University Union Hospital, Fuzhou, China[8]Jilin Provincial Tumor Hospital, Changchun, China[9]Jiangsu Cancer Hospital, Nanjing, China[10]The People’s Hospital of Peking University, Beijing, China[11]Shanghai Pulmonary Hospital, Tongji University, Shanghai, China[12]Tangdu Hospital, Xi’an, China[13]Peking University First Hospital, Beijing, China[14]Fujian Cancer Hospital, Fuzhou, China[15]Beijing Chest Hospital, Beijing, China[16]The First Hospital of China Medical University, Shenyang, China[17]Beijing Cancer Hospital, Beijing, China[18]Harbin Medical University Cancer Hospital, Harbin, China[19]West China Hospital of Sichuan University, Chengdu, China四川大学华西医院[20]Sichuan Cancer Hospital, Chengdu, China四川省肿瘤医院[21]The Northern Jiangsu People’s Hospital, Yangzhou, China江苏省人民医院[22]The First Affiliated Hospital of Suzhou University, Suzhou, China
Background Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II-IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with EGFR-mutant stage IB-IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II-IIIA (N1-N2) NSCLC. Methods We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18-75 years with completely resected (R0), stage II-IIIA (N1-N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1: 1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m(2) on days 1 and 8) plus intravenous cisplatin (75 mg/m(2) on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079. Findings Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36 . 5 months (IQR 23 . 8-44 . 8). Median disease-free survival was significantly longer with gefitinib (28 . 7 months [95% CI 24 . 9-32 . 5]) than with vinorelbine plus cisplatin (18 . 0 months [13 . 6-22 . 3]; hazard ratio [HR] 0 . 60, 95% CI 0 . 42-0 . 87; p=0 . 0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two [2%] patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 [34%] patients vs none with gefitinib), leucopenia (14 [16%] vs none), and vomiting (eight [9%] vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related. Interpretation Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II-IIIA (N1-N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature.
基金：
This study was funded by the Guangdong Provincial Key Laboratory of
Lung Cancer Translational Medicine (2012A061400006), National Health
and Family Planning Commission of China (201402031), Guangzhou
Science and Technology Bureau (2011Y2-00014 and 2014Y2-00545, to
Y-LW), AstraZeneca Pharmaceuticals, and the Chinese Thoracic
Oncology Group (CTONG). Medical writing support was provided by
Mark Holland (Complete Medical Communications) and funded by CTONG and AstraZeneca China.
第一作者机构：[1]Guangdong Lung Cancer Institute, Guangdong General Hospital, and Guangdong Academy of Medical Sciences, Guangzhou, China
通讯作者：
通讯机构：[1]Guangdong Lung Cancer Institute, Guangdong General Hospital, and Guangdong Academy of Medical Sciences, Guangzhou, China[*1]Guangdong Lung Cancer Institute, Guangdong General Hospital, and Guangdong Academy of Medical Sciences, Yuexiu Qu, Guangzhou 510080, China
推荐引用方式(GB/T 7714)：
Wen-Zhao Zhong,Qun Wang,Wei-Min Mao,et al.Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study[J].LANCET ONCOLOGY.2018,19(1):139-148.doi:10.1016/S1470-2045(17)30729-5.
APA：
Wen-Zhao Zhong,Qun Wang,Wei-Min Mao,Song-Tao Xu,Lin Wu...&the ADJUVANT investigators.(2018).Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study.LANCET ONCOLOGY,19,(1)
MLA：
Wen-Zhao Zhong,et al."Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study".LANCET ONCOLOGY 19..1(2018):139-148
医学