Tislelizumab Plus Chemotherapy vs Chemotherapy Alone as First-line Treatment for Advanced Squamous Non-Small-Cell Lung Cancer A Phase 3 Randomized Clinical Trial

被引:296
作者
Wang, Jie [1 ]
Lu, Shun [2 ]
Yu, Xinmin [3 ]
Hu, Yanping [4 ]
Sun, Yuping [5 ]
Wang, Zhijie [1 ]
Zhao, Jun [6 ]
Yu, Yan [7 ]
Hu, Chunhong [8 ]
Yang, Kunyu [9 ]
Feng, Guosheng [10 ]
Ying, Kejing [11 ]
Zhuang, Wu [12 ]
Zhou, Jianying [13 ]
Wu, Jingxun [14 ]
Leaw, Shiang Jiin [15 ]
Zhang, Jing [15 ]
Lin, Xiao [15 ]
Liang, Liang [15 ]
Yang, Nong [16 ]
机构
[1] Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Mol Oncol, Dept Med Oncol, Natl Canc Ctr,Natl Clin Res Ctr Canc,Canc Hosp, 17 Pan Jia Yuan South Lane, Beijing 100021, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Lung Canc Ctr, Shanghai Chest Hosp, Shanghai, Peoples R China
[3] Zhejiang Canc Hosp, Hangzhou, Peoples R China
[4] Hubei Canc Hosp, Wuhan, Peoples R China
[5] Jinan Cent Hosp, Jinan, Shandong, Peoples R China
[6] Peking Univ Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res, Minist Educ, Dept Thorac Med Oncol, Beijing, Peoples R China
[7] Harbin Med Univ Canc Hosp, Harbin, Peoples R China
[8] Cent South Univ, Second Hosp, Changsha, Peoples R China
[9] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Wuhan, Hubei, Peoples R China
[10] Peoples Hosp Guangxi Zhuang Autonomous Reg, Nanning, Guangxi Zhuang, Peoples R China
[11] Zhejiang Univ, Sir Run Shaw Hosp, Sch Med, Hangzhou, Zhejiang, Peoples R China
[12] Fujian Tumor Hosp, Fuzhou, Peoples R China
[13] Zhejiang Univ, Affiliated Hosp 1, Hangzhou, Zhejiang, Peoples R China
[14] Xiamen Univ, Affiliated Hosp 1, Xiamen, Fujian, Peoples R China
[15] BeiGene Beijing Co Ltd, Beijing, Peoples R China
[16] Cent South Univ, Dept Med Oncol, Lung Canc & Gastrointestinal Unit, Hunan Canc Hosp,Affiliated Canc Hosp,Xiangya Sch, Changsha, Peoples R China
关键词
NAB-PACLITAXEL; COMBINATION; CARBOPLATIN; THERAPY;
D O I
10.1001/jamaoncol.2021.0366
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
IMPORTANCE This study demonstrates that tislelizumab in combination with chemotherapy is associated with improved progression-free survival (PFS) in patients with advanced squamous non-small-cell lung cancer (sq-NSCLC). OBJECTIVE To assess the efficacy and safety/tolerability of tislelizumab plus chemotherapy vs chemotherapy alone as first-line treatment for patients with advanced sq-NSCLC. DESIGN, SETTING, AND PARTICIPANTS This open-label, randomized phase 3 clinical trial was conducted at 46 sites in China between July 2018 and June 2019 and included patients with treatment-naive, histologically confirmed stage IIIB/IV sq-NSCLC. The data cutoff for these analyses was December 6, 2019; data extraction occurred on January 7, 2020. INTERVENTIONS Patients were randomized (1:1:1) to receive 1 of the following regimens intravenously on a 21-day cycle: tislelizumab (200 mg, day 1) plus paclitaxel (175 mg/m(2), day 1) and carboplatin (area under the concentration of 5, day 1) (arm A); tislelizumab plus nab-paclitaxel (100 mg/m(2), days 1, 8, and 15) and carboplatin (arm B); and paclitaxel and carboplatin (arm C). Patients were stratified by disease stage and tumor programmed cell death 1 ligand 1 (PD-L1) expression (<1% vs 1%-49% vs >= 50%). MAIN OUTCOMES AND MEASURES The primary end point was progression-free survival (PFS) assessed by an independent review committee (IRC). Secondary end points included overall survival, investigator-assessed (INV) PFS, IRC-assessed objective response rate (ORR), and IRC-assessed duration of response, as well as the incidence and severity of adverse events (AEs). RESULTS Overall, 355 patients (median [range] age, 62 [34-74] years; 330 men [91.7%]) with sq-NSCLC received treatment. After a median study follow-up of 8.6 months (95% CI, 8.1-9.0 months), IRC-assessed PFS was significantly improved with tislelizumab plus chemotherapy (arm A, 7.6 months; arm B, 7.6 months) vs chemotherapy alone (arm C, 5.5 months; hazard ratios were 0.524 (95% CI, 0.370-0.742; P < .001 [A vs C]) and 0.478 (95% CI, 0.336-0.679; P < .001 [B vs C]). Higher IRC-assessed ORR and longer IRC-assessed duration of response were observed in arms A (72.5%; 8.2 months) and B (74.8%; 8.6 months) vs C (49.6%; 4.2 months). No association was observed between PD-L1 expression and IRC-assessed PFS or ORR. Discontinuation of any treatment because of AEs was reported in 15 (12.5%; arm A), 35 (29.7%; arm B), and 18 (15.4%; arm C) patients. In each arm, the most common grade of 3 or greater AE was decreased neutrophil levels, which aligned with known chemotherapy toxic effects. Six treatment-related AEs leading to death occurred; however, no deaths were solely attributed to tislelizumab. CONCLUSIONS AND RELEVANCE In this phase 3 randomized clinical trial, adding tislelizumab to chemotherapy was associated with significantly prolonged IRC-assessed PFS, higher IRC-assessed ORRs, and a manageable safety/tolerability profile in patients with advanced sq-NSCLC, regardless of PD-L1 expression.
引用
收藏
页码:709 / 717
页数:9
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