Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): a randomised, open-label, multicentre, phase 3 trial

被引:348
作者
Zhou, Caicun [1 ]
Chen, Gongyan [2 ]
Huang, Yunchao [3 ,4 ,5 ]
Zhou, Jianying [6 ]
Lin, LiZhu [7 ]
Feng, Jifeng [8 ,9 ,10 ]
Wang, Zhehai [11 ]
Shu, Yongqian [12 ]
Shi, Jianhua [13 ]
Hu, Yi [14 ]
Wang, QiMing [15 ]
Cheng, Ying [16 ]
Wu, Fengying [1 ]
Chen, Jianhua [17 ]
Lin, Xiaoyan [18 ]
Wang, Yongsheng [19 ]
Huang, Jianan [20 ]
Cui, Jiuwei [21 ]
Cao, Lejie [22 ]
Liu, Yunpeng [24 ]
Zhang, Yiping [25 ]
Pan, Yueyin [23 ]
Zhao, Jun [26 ]
Wang, LiPing [28 ]
Chang, Jianhua [29 ]
Chen, Qun [30 ]
Ren, Xiubao [31 ]
Zhang, Wei [32 ]
Fan, Yun [25 ]
He, Zhiyong [33 ]
Fang, Jian [27 ]
Gu, Kangsheng [34 ]
Dong, XiaoRong [35 ]
Zhang, Tao [36 ]
Shi, Wei [36 ]
Zou, Jianjun [36 ]
机构
[1] Tongji Univ, Shanghai Pulm Hosp, Dept Med Oncol, Shanghai 200433, Peoples R China
[2] Harbin Med Univ Canc Hosp, Dept Resp Med, Harbin, Peoples R China
[3] Kunming Med Univ, Dept Thorac Surg Oncol, Yunnan Canc Hosp, Kunming, Yunnan, Peoples R China
[4] Kunming Med Univ, Affiliated Hosp 3, Kunming, Yunnan, Peoples R China
[5] Yunnan Canc Ctr, Kunming, Yunnan, Peoples R China
[6] Zhejiang Univ, Resp Med, Affiliated Hosp 1, Hangzhou, Peoples R China
[7] Guangzhou Univ Chinese Med, Oncol Ctr, Affiliated Hosp 1, Guangzhou, Peoples R China
[8] Nanjing Med Univ, Dept Thorac Med Oncol, Jiangsu Canc Hosp, Nanjing, Peoples R China
[9] Nanjing Med Univ, Jiangsu Inst Canc Res, Nanjing, Peoples R China
[10] Nanjing Med Univ, Affiliated Canc Hosp, Nanjing, Peoples R China
[11] Shandong Canc Hosp & Inst, Dept Resp, Jinan, Peoples R China
[12] Jiangsu Prov Hosp, Dept Oncol, Nanjing, Peoples R China
[13] Linyi Canc Hosp, Dept Med Oncol, Linyi, Shandong, Peoples R China
[14] Chinese Peoples Liberat Army, Oncol Dept, Gen Hosp, Beijing, Peoples R China
[15] Henan Canc Hosp, Resp Med, Zhengzhou, Peoples R China
[16] Jilin Canc Hosp, Dept Thorac Oncol, Changchun, Peoples R China
[17] Hunan Canc Hosp, Dept Med Oncol Chest, Changsha, Peoples R China
[18] Fujian Med Univ Union Hosp, Dept Oncol, Fuzhou, Peoples R China
[19] Sichuan Univ, West China Hosp, Dept Thorac Med Oncol, Chengdu, Peoples R China
[20] Suzhou Univ, Dept Respirat, Affiliated Hosp 1, Suzhou, Peoples R China
[21] Jilin Univ, Dept Med Oncol, First Bethune Hosp, Changchun, Peoples R China
[22] Univ Sci Technol China, Affiliated Hosp 1, Pulm & Crit Care Med, Hefei, Peoples R China
[23] Univ Sci Technol China, Affiliated Hosp 1, Dept Tumor Chemotherapy, Hefei, Peoples R China
[24] China Med Univ, Dept Med Oncol, Hosp 1, Shenyang, Peoples R China
[25] Zhejiang Canc Hosp, Dept Thorac Med Oncol, Hangzhou, Peoples R China
[26] Peking Univ, Dept Thoraac Med Oncol, Canc Hosp & Inst, Beijing, Peoples R China
[27] Peking Univ, Dept Thorac Oncol 2, Key Lab Carcinogenesis AndTranslat Res, Minist Educ Beijing, Beijing, Peoples R China
[28] Zhengzhou Univ, Dept Med Oncol, Affiliated Hosp 1, Zhengzhou, Peoples R China
[29] Fudan Univ, Dept Med Oncol, Shanghai Canc Ctr, Shanghai, Peoples R China
[30] Fuzhou Pulm Hosp Fujian, Dept Oncol, Fuzhou, Peoples R China
[31] Tianjin Med Univ Canc Inst & Hosp, Dept Biotherapy, Tianjin, Peoples R China
[32] Nanchang Univ, Pneumol Dept, Affiliated Hosp 1, Nanchang, Jiangxi, Peoples R China
[33] Fujian Canc Hosp, Dept Thorac Oncol, Fuzhou, Peoples R China
[34] Anhui Med Univ, Dept Med Oncol, Affiliated Hosp 1, Hefei, Peoples R China
[35] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Canc Ctr, Wuhan, Peoples R China
[36] Jiangsu Hengrui Med, Clin Res & Dev, Shanghai, Peoples R China
关键词
PEMBROLIZUMAB; BEVACIZUMAB; PLACEBO; TMB; KEYNOTE-021; CARCINOMA; OUTCOMES; THERAPY; SAFETY;
D O I
10.1016/S2213-2600(20)30365-9
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Background Immunotherapy combined with chemotherapy has been shown to be efficacious as treatment for advanced non-squamous non-small-cell lung cancer (NSCLC) without targetable genetic aberrations; however, there is scarce evidence of the effectiveness of the combinations in the Asian population. We evaluated camrelizumab plus chemotherapy against non-squamous NSCLC in China. Methods We did a randomised, open-label, multicentre, phase 3 trial (CameL) in 52 hospitals in China for patients with non-squamous NSCLC without EGFR and ALK alteration. Eligible patients were aged 18-70 years and had no previous systemic chemotherapy, Eastern Cooperative Oncology Group performance status of 0 or 1, and at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (version 1.1). Patients were randomly assigned (1:1) to receive 4-6 cycles of carboplatin (area under curve 5 mg/mL per min) plus pemetrexed (500 mg/m(2)) with or without camrelizumab (200 mg) every 3 weeks, followed by maintenance therapy with camrelizumab plus pemetrexed or pemetrexed alone. Medication was administered intravenously on day 1 of each 3-week treatment cycle. Randomisation was done using a centralised interactive web-response system with the block size randomly generated as four or six and stratified by sex and smoking history. The two primary endpoints were progression-free survival per blinded independent central review, in all patients and in patients who were PD-L1 positive. Primary analysis was done in the full analysis set that included all randomly assigned patients who received at least one dose of the study treatment. Herein, due to the primary endpoint being met at the interim analysis, we reported the findings of prespeci.ed interim analysis, which only included confirmatory statistical testing for progression-free survival in all patients. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov, NCT03134872 (follow-up is ongoing). Findings Between May 12, 2017, and June 6, 2018, of the 419 patients who were randomly assigned, seven did not receive assigned treatment and 412 received either camrelizumab plus chemotherapy (n=205) or chemotherapy alone (n=207). At interim analysis, median follow-up duration was 11.9 months (IQR 9.0-14.9). Progression-free survival in this interim analysis was significantly prolonged with camrelizumab plus chemotherapy than with chemotherapy alone (median 11.3 months [95% CI 9.6-15.4] vs 8.3 months [6.0-9.7]; hazard ratio 0.60 [0.45-0.79]; one-sided p=0.0001). Most common grade 3 or worse treatment-related adverse events were decreased neutrophil count (78 [38%] patients in the camrelizumab plus chemotherapy group vs 63 [30%] patients in the chemotherapy alone group), decreased white blood cell count (40 [20%] vs 30 [14%]), anaemia (38 [19%] vs 23 [11%]), and decreased platelet count (34 [17%] vs 24 [12%]). Serious treatment-related adverse events occurred in 74 (36%) patients in the camrelizumab plus chemotherapy group and 27 (13%) patients in the chemotherapy alone group. Interpretation The primary endpoint was met at the interim analysis, showing a statistically significant and clinically meaningful improvement in progression-free survival with camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in all patients, supporting camrelizumab plus carboplatin and pemetrexed as a first-line treatment option for Chinese patients with advanced non-squamous NSCLC without EGFR and ALK alterations. The trial is being continued to collect long-term outcomes in all patients and carry out confirmatory statistical testing for progression-free survival in the PD-L1-positive population.
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页码:305 / 314
页数:10
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