Gustave Roussy, Department of Medical Oncology, Thoracic Group, Villejuif, France.
Asklepios Lung Clinic, Munich-Gauting, Germany.
Ann Oncol. 2020 May;31(5):609-618. doi: 10.1016/j.annonc.2020.02.006. Epub 2020 Feb 20.
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.
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).
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).
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.
Clinicaltrials.gov identifier: NCT02352948.
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。
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）。
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）。
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。
Clinicaltrials.gov 标识符：NCT02352948。
