PMID- 33792623 OWN - NLM STAT- MEDLINE DCOM- 20220311 LR - 20220423 IS - 2374-2445 (Electronic) IS - 2374-2437 (Print) IS - 2374-2437 (Linking) VI - 7 IP - 5 DP - 2021 May 1 TI - Tislelizumab Plus Chemotherapy vs Chemotherapy Alone as First-line Treatment for Advanced Squamous Non-Small-Cell Lung Cancer: A Phase 3 Randomized Clinical Trial. PG - 709-717 LID - 10.1001/jamaoncol.2021.0366 [doi] AB - 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/m2, day 1) and carboplatin (area under the concentration of 5, day 1) (arm A); tislelizumab plus nab-paclitaxel (100 mg/m2, 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03594747. FAU - Wang, Jie AU - Wang J AD - State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Lu, Shun AU - Lu S AD - Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Yu, Xinmin AU - Yu X AD - Zhejiang Cancer Hospital, Hangzhou, China. FAU - Hu, Yanping AU - Hu Y AD - Hubei Cancer Hospital, Wuhan, China. FAU - Sun, Yuping AU - Sun Y AD - Jinan Central Hospital, Shandong, China. FAU - Wang, Zhijie AU - Wang Z AD - State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Zhao, Jun AU - Zhao J AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Thoracic Medical Oncology, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Yu, Yan AU - Yu Y AD - Harbin Medical University Cancer Hospital, Harbin, China. FAU - Hu, Chunhong AU - Hu C AD - The Second Hospital of Central South University, Changsha, China. FAU - Yang, Kunyu AU - Yang K AD - Union Hospital Tongji Medical College Huazhong University of Science and Technology, Hubei, China. FAU - Feng, Guosheng AU - Feng G AD - The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China. FAU - Ying, Kejing AU - Ying K AD - Sir Run Shaw Hospital, Zhejiang University, School of Medicine, Zhejiang, China. FAU - Zhuang, Wu AU - Zhuang W AD - Fujian Tumor Hospital, Fuzhou, China. FAU - Zhou, Jianying AU - Zhou J AD - The First Affiliated Hospital, Zhejiang University, Zhejiang, China. FAU - Wu, Jingxun AU - Wu J AD - The First Affiliated Hospital of Xiamen University, Fujian, China. FAU - Leaw, Shiang Jiin AU - Leaw SJ AD - BeiGene (Beijing) Co, Ltd, Beijing, China. FAU - Zhang, Jing AU - Zhang J AD - BeiGene (Beijing) Co, Ltd, Beijing, China. FAU - Lin, Xiao AU - Lin X AD - BeiGene (Beijing) Co, Ltd, Beijing, China. FAU - Liang, Liang AU - Liang L AD - BeiGene (Beijing) Co, Ltd, Beijing, China. FAU - Yang, Nong AU - Yang N AD - Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China. LA - eng SI - ClinicalTrials.gov/NCT03594747 PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Oncol JT - JAMA oncology JID - 101652861 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0KVO411B3N (tislelizumab) RN - BG3F62OND5 (Carboplatin) RN - P88XT4IS4D (Paclitaxel) SB - IM CIN - JAMA Oncol. 2021 May 1;7(5):717-719. PMID: 33792622 CIN - JAMA Oncol. 2021 Oct 1;7(10):1580-1581. PMID: 34410312 CIN - JAMA Oncol. 2021 Oct 1;7(10):1580. PMID: 34410318 MH - Antibodies, Monoclonal, Humanized MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - Carboplatin/therapeutic use MH - *Carcinoma, Non-Small-Cell Lung/drug therapy/pathology MH - *Carcinoma, Squamous Cell/drug therapy MH - Humans MH - *Lung Neoplasms/pathology MH - Paclitaxel/adverse effects PMC - PMC8017481 COIS- Conflict of Interest Disclosures: Dr Lu reports research support from AstraZeneca, Hutchison, BMS, Heng Rui, and Roche; speaker fees from AstraZeneca, Roche, and Hansoh; and advisor/consultant fees from AstraZeneca, Boehringer Ingelheim, Hutchison MediPharma, Simcere, ZaiLab, GenomiCare, and Roche. Drs Leaw, Zhao, Lin, and Liang report being employees of BeiGene. No other disclosures were reported. EDAT- 2021/04/02 06:00 MHDA- 2022/03/12 06:00 PMCR- 2021/04/01 CRDT- 2021/04/01 12:31 PHST- 2021/04/02 06:00 [pubmed] PHST- 2022/03/12 06:00 [medline] PHST- 2021/04/01 12:31 [entrez] PHST- 2021/04/01 00:00 [pmc-release] AID - 2777901 [pii] AID - coi210004 [pii] AID - 10.1001/jamaoncol.2021.0366 [doi] PST - ppublish SO - JAMA Oncol. 2021 May 1;7(5):709-717. doi: 10.1001/jamaoncol.2021.0366.