Cancer Communications (Dec 2022)

Sintilimab versus docetaxel as second‐line treatment in advanced or metastatic squamous non‐small‐cell lung cancer: an open‐label, randomized controlled phase 3 trial (ORIENT‐3)

  • Yuankai Shi,
  • Lin Wu,
  • Xinmin Yu,
  • Puyuan Xing,
  • Yan Wang,
  • Jianying Zhou,
  • Airong Wang,
  • Jianhua Shi,
  • Yi Hu,
  • Ziping Wang,
  • Guangyu An,
  • Yong Fang,
  • Sanyuan Sun,
  • Caicun Zhou,
  • Changli Wang,
  • Feng Ye,
  • Xingya Li,
  • Junye Wang,
  • Mengzhao Wang,
  • Yunpeng Liu,
  • Yanqiu Zhao,
  • Ying Yuan,
  • Jifeng Feng,
  • Zhendong Chen,
  • Jindong Shi,
  • Tao Sun,
  • Gang Wu,
  • Yongqian Shu,
  • Qisen Guo,
  • Yi Zhang,
  • Yong Song,
  • Shucai Zhang,
  • Yuan Chen,
  • Wei Li,
  • Hongrui Niu,
  • Wenwei Hu,
  • Lijun Wang,
  • Jianan Huang,
  • Yang Zhang,
  • Ying Cheng,
  • Zhengdong Wu,
  • Bo Peng,
  • Jiya Sun,
  • Christoph Mancao,
  • Yanqi Wang,
  • Luyao Sun

DOI
https://doi.org/10.1002/cac2.12385
Journal volume & issue
Vol. 42, no. 12
pp. 1314 – 1330

Abstract

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Abstract Background Treatment options for Chinese patients with locally advanced or metastatic squamous‐cell non‐small‐cell lung cancer (sqNSCLC) after failure of first‐line chemotherapy are limited. This study (ORIENT‐3) aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second‐line treatment in patients with locally advanced or metastatic sqNSCLC. Methods ORIENT‐3 was an open‐label, multicenter, randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first‐line platinum‐based chemotherapy. Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m2 of docetaxel intravenously every 3 weeks, stratified by the Eastern Cooperative Oncology Group performance status. The primary endpoint was overall survival (OS) in the full analysis set (FAS). Secondary endpoints included progression‐free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety. Results Between August 25, 2017, and November 7, 2018, 290 patients were randomized. For FAS, 10 patients from the docetaxel arm were excluded. The median OS was 11.79 (n = 145; 95% confidence interval [CI], 10.28‐15.57) months with sintilimab versus 8.25 (n = 135; 95% CI, 6.47‐9.82) months with docetaxel (hazard ratio [HR]: 0.74; 95% CI, 0.56‐0.96; P = 0.025). Sintilimab treatment significantly prolonged PFS (median 4.30 vs. 2.79 months; HR: 0.52; 95% CI, 0.39‐0.68; P < 0.001) and showed higher ORR (25.50% vs. 2.20%, P < 0.001) and DCR (65.50% vs. 37.80%, P < 0.001) than the docetaxel arm. The median DoR was 12.45 (95% CI, 4.86‐25.33) months in the sintilimab arm and 4.14 (95% CI, 1.41‐7.23) months in the docetaxel arm (P = 0.045). Treatment‐related adverse events of grade ≥ 3 were reported in 26 (18.1%) patients in the sintilimab arm and 47 (36.2%) patients in the docetaxel arm. Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors, including OVOL2 (HR: 0.35; P < 0.001) and CTCF (HR: 3.50; P < 0.001)，for sintilimab treatment. Conclusions Compared with docetaxel, sintilimab significantly improved the OS, PFS, and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC.

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