Details

Autor(en) / Beteiligte

• Zhou, Caicun
• Wu, Lin
• Fan, Yun
• Wang, Zhehai
• Liu, Lianke
• Chen, Gongyan
• Zhang, Li
• Huang, Dingzhi
• Cang, Shundong
• Yang, Zhixiong
• Zhou, Jianying
• Zhou, Chengzhi
• Li, Baolan
• Li, Juan
• Fan, Min
• Cui, Jiuwei
• Li, Yuping
• Zhao, Hui
• Fang, Jian
• Xue, Jianxin
• Hu, Chengping
• Sun, Ping
• Du, Yingying
• Zhou, Hui
• Wang, Shuyan
• Zhang, Wen

Titel

Sintilimab Plus Platinum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results From a Randomized, Double-Blind, Phase 3 Trial (ORIENT-12)

Ist Teil von

• Journal of thoracic oncology, 2021-09, Vol.16 (9), p.1501-1511

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• The standard chemotherapy for squamous NSCLC (sqNSCLC) includes platinum plus gemcitabine. Sintilimab, an anti–programmed cell death protein 1 antibody, plus platinum and gemcitabine (GP) has revealed encouraging efficacy as first-line therapy for sqNSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to further compare the efficacy and safety of sintilimab with placebo, both in combination with GP. ORIENT-12, a randomized, double-blind, phase 3 study, was conducted at 42 centers in the People’s Republic of China (ClinicalTrials.gov, number NCT03629925). Patients with locally advanced or metastatic sqNSCLC and without EGFR-sensitive mutations or ALK rearrangements were enrolled in the study. The stratification factors included clinical stage, choice of platinum, and programmed death-ligand 1 tumor proportion score. The patients, investigators, research staff, and sponsor team were masked to treatment assignment. Eligible patients were randomized 1:1, using an integrated web-response system, to receive sintilimab 200 mg or placebo plus GP every 3 weeks for four or six cycles, followed by sintilimab or placebo as maintenance therapy until disease progression or 2 years. The primary end point was progression-free survival (PFS), assessed by an independent radiographic review committee. Between September 25, 2018 and July 26, 2019, a total of 543 patients were screened, of whom 357 patients were randomized to the sintilimab-GP group (n = 179) and the placebo-GP group (n = 178). After a median follow-up period of 12.9 months, sintilimab-GP continued to reveal a meaningful improvement in PFS than placebo-GP (hazard ratio = 0.536 [95% confidence interval: 0.422–0.681], p < 0.00001). Treatment-emergent adverse events of grade 3 or worse occurred in 86.6% patients in the sintilimab-GP group and in 83.1% in the placebo-GP group. The incidence of treatment-emergent adverse event leading to death was 4.5% and 6.7% in the two treatment groups, respectively. Regarding PFS, sintilimab plus GP reveals clinical benefit than GP alone as first-line therapy in patients with locally advanced or metastatic sqNSCLC. The toxicity was acceptable, and no new unexpected safety signals were observed.