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

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

  • JAMA Oncol. 2021 May 1;7(5):709-717. doi: 10.1001/jamaoncol.2021.0366.
Jie Wang 1,  Shun Lu 2,  Xinmin Yu 3,  Yanping Hu 4,  Yuping Sun 5,  Zhijie Wang 1,  Jun Zhao 6,  Yan Yu 7,  Chunhong Hu 8,  Kunyu Yang 9,  Guosheng Feng 10,  Kejing Ying 11,  Wu Zhuang 12,  Jianying Zhou 13,  Jingxun Wu 14,  Shiang Jiin Leaw 15,  Jing Zhang 15,  Xiao Lin 15,  Liang Liang 15,  Nong Yang 16
Affiliations

Affiliations

  • 1 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.
  • 2 Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
  • 3 Zhejiang Cancer Hospital, Hangzhou, China.
  • 4 Hubei Cancer Hospital, Wuhan, China.
  • 5 Jinan Central Hospital, Shandong, China.
  • 6 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Thoracic Medical Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
  • 7 Harbin Medical University Cancer Hospital, Harbin, China.
  • 8 The Second Hospital of Central South University, Changsha, China.
  • 9 Union Hospital Tongji Medical College Huazhong University of Science and Technology, Hubei, China.
  • 10 The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
  • 11 Sir Run Shaw Hospital, Zhejiang University, School of Medicine, Zhejiang, China.
  • 12 Fujian Tumor Hospital, Fuzhou, China.
  • 13 The First Affiliated Hospital, Zhejiang University, Zhejiang, China.
  • 14 The First Affiliated Hospital of Xiamen University, Fujian, China.
  • 15 BeiGene (Beijing) Co, Ltd, Beijing, China.
  • 16 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.
PMID: 33792623 DOI: 10.1001/jamaoncol.2021.0366
Abstract

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.

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