Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): multicentre, randomised, double blind, phase 3 trial.
Abstract | OBJECTIVE: DESIGN: Multicentre, randomised, double blind, phase 3 trial. SETTING: 66 sites in China and 13 sites outside of China between 14 December 2018 and 9 April 2021. PARTICIPANTS: INTERVENTION: MAIN OUTCOME MEASURES: Overall survival in all patients and in patients with combined positive scores of ≥10 for expression of programmed cell death ligand 1. RESULTS: 659 patients were randomly assigned to sintilimab (n=327) or placebo (n=332) with chemotherapy. 616 of 659 patients (93%) received sintilimab or placebo in combination with cisplatin plus paclitaxel and 43 of 659 patients (7%) received sintilimab or placebo in combination with cisplatin plus 5-fluorouracil. At the interim analysis, sintilimab with chemotherapy showed better overall survival compared with placebo and chemotherapy in all patients (median 16.7 v 12.5 months, hazard ratio 0.63, 95% confidence interval 0.51 to 0.78, P<0.001) and in patients with combined positive scores of ≥10 (17.2 v 13.6 months, 0.64, 0.48 to 0.85, P=0.002). Sintilimab and chemotherapy significantly improved progression free survival compared with placebo and chemotherapy in all patients (7.2 v 5.7 months, 0.56, 0.46 to 0.68, P<0.001) and in patients with combined positive scores of ≥10 (8.3 v 6.4 months, 0.58, 0.45 to 0.75, P<0.001). Adverse events related to treatment occurred in 321 of 327 patients (98%) in the sintilimab- chemotherapy group versus 326 of 332 (98%) patients in the placebo- chemotherapy group. Rates of adverse events related to treatment, grade ≥3, were 60% (196/327) and 55% (181/332) in the sintilimab- chemotherapy and placebo- chemotherapy groups, respectively. CONCLUSIONS: TRIAL REGISTRATION: ClinicalTrials.gov NCT03748134.
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Authors | Zhihao Lu, Junye Wang, Yongqian Shu, Lianke Liu, Li Kong, Lei Yang, Buhai Wang, Guogui Sun, Yinghua Ji, Guochun Cao, Hu Liu, Tongjian Cui, Na Li, Wensheng Qiu, Gaofeng Li, Xinfang Hou, Hui Luo, Liying Xue, Yanqiao Zhang, Wenbin Yue, Zheng Liu, Xiuwen Wang, Shegan Gao, Yueyin Pan, Marie-Pierre Galais, Aziz Zaanan, Zhuo Ma, Haoyu Li, Yan Wang, Lin Shen, ORIENT-15 study group |
Journal | BMJ (Clinical research ed.)
(BMJ)
Vol. 377
Pg. e068714
(04 19 2022)
ISSN: 1756-1833 [Electronic] England |
PMID | 35440464
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
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Copyright | © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. |
Chemical References |
- Antibodies, Monoclonal, Humanized
- sintilimab
- Paclitaxel
- Cisplatin
- Fluorouracil
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Topics |
- Adolescent
- Adult
- Antibodies, Monoclonal, Humanized
(adverse effects)
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects)
- Cisplatin
(therapeutic use)
- Double-Blind Method
- Esophageal Neoplasms
(drug therapy)
- Esophageal Squamous Cell Carcinoma
(drug therapy)
- Fluorouracil
(therapeutic use)
- Humans
- Paclitaxel
(therapeutic use)
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