信迪利单抗对比多西他赛用于晚期或转移性鳞状非小细胞肺癌二线治疗：一项开放标签、随机对照的 3 期临床试验（ORIENT-3）。
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).
机构信息
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, P. R. China.
Department II of Thoracic Medicine, Hunan Cancer Hospital, Changsha, Hunan, P. R. China.
出版信息
Cancer Commun (Lond). 2022 Dec;42(12):1314-1330. doi: 10.1002/cac2.12385. Epub 2022 Nov 6.
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/m 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.
背景
一线化疗失败后，中国局部晚期或转移性鳞状非小细胞肺癌（sqNSCLC）患者的治疗选择有限。本研究（ORIENT-3）旨在评估信迪利单抗对比多西他赛作为局部晚期或转移性 sqNSCLC 二线治疗的疗效和安全性。
方法
ORIENT-3 是一项开放标签、多中心、随机对照的 3 期临床试验，招募了一线含铂化疗失败的局部晚期/不可切除 IIIB/IIIC/IV 期 sqNSCLC 患者。患者按东部肿瘤协作组体力状况（ECOG PS）分层，以 1:1 的比例随机接受 200mg 信迪利单抗或 75mg/m2 多西他赛静脉输注，每 3 周一次。主要终点为全分析集（FAS）的总生存期（OS）。次要终点包括无进展生存期（PFS）、客观缓解率（ORR）、疾病控制率（DCR）、缓解持续时间（DoR）和安全性。
结果
2017 年 8 月 25 日至 2018 年 11 月 7 日期间，共招募了 290 例患者。FAS 中，10 例多西他赛组患者被排除。信迪利单抗组的中位 OS 为 11.79 个月（n=145；95%置信区间 [CI]，10.28-15.57），而多西他赛组为 8.25 个月（n=135；95% CI，6.47-9.82）（风险比 [HR]：0.74；95% CI，0.56-0.96；P=0.025）。信迪利单抗治疗显著延长了 PFS（中位 4.30 个月 vs. 2.79 个月；HR：0.52；95% CI，0.39-0.68；P<0.001），并显示出更高的 ORR（25.50% vs. 2.20%，P<0.001）和 DCR（65.50% vs. 37.80%，P<0.001），优于多西他赛组。信迪利单抗组的中位 DoR 为 12.45 个月（95% CI，4.86-25.33），多西他赛组为 4.14 个月（95% CI，1.41-7.23）（P=0.045）。信迪利单抗组有 26 例（18.1%）和多西他赛组有 47 例（36.2%）患者发生≥3 级治疗相关不良事件。探索性生物标志物分析显示，两个转录因子的表达水平可能对信迪利单抗治疗有预测价值，包括 OVOL2（HR：0.35；P<0.001）和 CTCF（HR：3.50；P<0.001）。
结论
与多西他赛相比，信迪利单抗显著改善了中国局部晚期或转移性 sqNSCLC 患者的 OS、PFS 和 ORR。
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