ARCTIC 研究：度伐利尤单抗联合或不联合替西木单抗作为转移性非小细胞肺癌三线或后线治疗。
ARCTIC: durvalumab with or without tremelimumab as third-line or later treatment of metastatic non-small-cell lung cancer.
机构信息
Gustave Roussy, Department of Medical Oncology, Thoracic Group, Villejuif, France.
Asklepios Lung Clinic, Munich-Gauting, Germany.
出版信息
Ann Oncol. 2020 May;31(5):609-618. doi: 10.1016/j.annonc.2020.02.006. Epub 2020 Feb 20.
BACKGROUND
Many patients with metastatic non-small-cell lung cancer (mNSCLC) experience disease progression after first- and second-line treatment; more treatment options are required for these patients. ARCTIC, a phase III, randomized, open-label study, assessed durvalumab ± tremelimumab versus standard of care (SoC) as ≥ third-line treatment of mNSCLC.
PATIENTS AND METHODS
ARCTIC comprised two independent sub-studies. Study A: 126 patients with ≥25% of tumor cells (TCs) expressing programmed cell death ligand-1 (PD-L1) were randomized (1 : 1) to durvalumab [up to 12 months 10 mg/kg every 2 weeks (q2w)] or SoC. Study B: 469 patients with PD-L1 TC <25% were randomized (3 : 2 : 2 : 1) to durvalumab + tremelimumab (12 weeks durvalumab 20 mg/kg + tremelimumab 1 mg/kg q4w then 34 weeks durvalumab 10 mg/kg q2w), SoC, durvalumab (up to 12 months 10 mg/kg q2w), or tremelimumab (24 weeks 10 mg/kg q4w then 24 weeks q12w). Primary end points: overall survival (OS) and progression-free survival (PFS) for durvalumab versus SoC (study A; descriptive only) and durvalumab + tremelimumab versus SoC (study B).
RESULTS
Study A: median OS 11.7 (durvalumab) versus 6.8 (SoC) months {hazard ratio (HR) 0.63 [95% confidence interval (CI), 0.42-0.93]}; median PFS 3.8 (durvalumab) versus 2.2 (SoC) months [HR 0.71 (95% CI, 0.49-1.04)]. Study B: median OS 11.5 (durvalumab + tremelimumab) versus 8.7 (SoC) months [HR 0.80 (95% CI, 0.61-1.05); P = 0.109]. Median PFS of 3.5 months for both groups [HR 0.77 (95% CI, 0.59-1.01); P = 0.056]. Treatment-related grade 3/4 adverse events: 9.7% (durvalumab) and 44.4% (SoC; study A) and 22.0% (durvalumab + tremelimumab) and 36.4% (SoC; study B).
CONCLUSIONS
In heavily pretreated patients with mNSCLC, durvalumab demonstrated clinically meaningful improvements in OS and PFS versus SoC (patients with PD-L1 TC ≥25%); numerical improvements in OS and PFS for durvalumab + tremelimumab versus SoC were observed (patients with PD-L1 TC <25%). Safety profiles were consistent with previous studies.
TRIAL REGISTRATION
Clinicaltrials.gov identifier: NCT02352948.
背景
许多转移性非小细胞肺癌（mNSCLC）患者在一线和二线治疗后出现疾病进展；这些患者需要更多的治疗选择。ARCTIC 是一项 III 期、随机、开放标签研究，评估了 durvalumab±tremelimumab 作为 mNSCLC 的≥三线治疗与标准治疗（SoC）相比的疗效。
患者和方法
ARCTIC 包括两项独立的子研究。研究 A：126 例肿瘤细胞（TCs）中≥25%表达程序性死亡配体-1（PD-L1）的患者按 1:1 随机分组（durvalumab：最多 12 个月，10 mg/kg，每 2 周 1 次[q2w]；SoC）。研究 B：469 例 PD-L1 TC <25%的患者按 3:2:2:1 随机分组（durvalumab+tremelimumab：12 周 durvalumab 20 mg/kg+tremelimumab 1 mg/kg，每 4 周 1 次[q4w]，然后 34 周 durvalumab 10 mg/kg，每 2 周 1 次[q2w]；SoC；durvalumab：最多 12 个月，10 mg/kg，每 2 周 1 次；tremelimumab：24 周 10 mg/kg，每 4 周 1 次，然后 24 周 1 次[q12w]）。主要终点：durvalumab 与 SoC 相比的总生存期（OS）和无进展生存期（PFS）（研究 A：仅描述性分析）和 durvalumab+tremelimumab 与 SoC 相比的 OS 和 PFS（研究 B）。
结果
研究 A：中位 OS 11.7（durvalumab）对比 6.8（SoC）个月[风险比（HR）0.63（95%置信区间[CI]，0.42-0.93）]；中位 PFS 3.8（durvalumab）对比 2.2（SoC）个月[HR 0.71（95% CI，0.49-1.04）]。研究 B：中位 OS 11.5（durvalumab+tremelimumab）对比 8.7（SoC）个月[HR 0.80（95% CI，0.61-1.05）；P=0.109]。两组中位 PFS 均为 3.5 个月[HR 0.77（95% CI，0.59-1.01）；P=0.056]。治疗相关的 3/4 级不良事件：9.7%（durvalumab）对比 44.4%（SoC；研究 A）和 22.0%（durvalumab+tremelimumab）对比 36.4%（SoC；研究 B）。
结论
在接受过多线治疗的 mNSCLC 患者中，与 SoC 相比，durvalumab 在 OS 和 PFS 方面表现出具有临床意义的改善（PD-L1 TC≥25%）；durvalumab+tremelimumab 与 SoC 相比，OS 和 PFS 有数值改善（PD-L1 TC<25%）。安全性与先前的研究一致。
临床试验注册
Clinicaltrials.gov 标识符：NCT02352948。
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