avelumab 对比含铂双药化疗作为 PD-L1 高表达转移性 NSCLC 患者一线治疗：来自 III 期 JAVELIN Lung 100 试验的主要分析。
Avelumab Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With High-Expression Programmed Death-Ligand 1-Positive Metastatic NSCLC: Primary Analysis From the Phase 3 JAVELIN Lung 100 Trial.
机构信息
LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.
Université Paris Saclay, Faculté de Médecine, Kremlin Bicêtre, France; Medical Oncology department, Gustave Roussy, Villejuif, France; Present Address: Université Paris Saclay, Faculté de Médecine, Kremlin Bicêtre, France; Medical Oncology Department, Gustave Roussy, Villejuif, France.
出版信息
J Thorac Oncol. 2024 Feb;19(2):297-313. doi: 10.1016/j.jtho.2023.09.1445. Epub 2023 Sep 24.
INTRODUCTION
We report the primary analysis from JAVELIN Lung 100, a phase 3 trial comparing avelumab (anti-programmed death-ligand 1 [PD-L1]) versus platinum-based doublet chemotherapy as first-line treatment for PD-L1-positive (+) advanced NSCLC.
METHODS
Adults with PD-L1+ (≥1% of tumor cells; PD-L1 immunohistochemistry 73-10 pharmDx), EGFR and ALK wild-type, previously untreated, stage IV NSCLC were randomized to avelumab 10 mg/kg every 2 weeks (Q2W), avelumab 10 mg/kg once weekly (QW) for 12 weeks and Q2W thereafter, or platinum-based doublet chemotherapy every 3 weeks. Primary end points were overall survival (OS) and progression-free survival (PFS) per independent review committee. The primary analysis population was patients with high-expression PD-L1+ tumors (≥80% of tumor cells).
RESULTS
A total of 1214 patients were randomized to avelumab Q2W (n = 366), avelumab QW (n = 322), or chemotherapy (n = 526). In the primary analysis population, hazard ratios (HRs) for OS and PFS with avelumab Q2W (n = 151) versus chemotherapy (n = 216) were 0.85 (95% confidence interval [CI]: 0.67-1.09; one-sided p = 0.1032; median OS, 20.1 versus 14.9 mo) and 0.71 (95% CI: 0.54-0.93; one-sided p = 0.0070; median PFS, 8.4 versus 5.6 mo), respectively. With avelumab QW (n = 130) versus chemotherapy (n = 129), HRs were 0.79 (95% CI: 0.59-1.07; one-sided p = 0.0630; median OS, 19.3 versus 15.3 mo) and 0.72 (95% CI: 0.52-0.98; one-sided p = 0.0196; median PFS, 7.5 versus 5.6 mo), respectively. No new safety signals were observed.
CONCLUSIONS
Longer median OS and PFS were observed with avelumab versus platinum-based doublet chemotherapy in advanced NSCLC, but differences in OS and PFS were not statistically significant, and the trial did not meet its primary objective.
CLINICALTRIALS
gov Identifier: NCT02576574.
简介
我们报告了 JAVELIN Lung 100 的主要分析结果，这是一项 3 期临床试验，比较了avelumab（抗程序性死亡配体 1 [PD-L1]）与铂类双联化疗作为 PD-L1 阳性（+）晚期 NSCLC 的一线治疗。
方法
未经治疗的 PD-L1+（肿瘤细胞的≥1%；PD-L1 免疫组化 73-10 pharmDx）、EGFR 和 ALK 野生型、先前未经治疗的 IV 期 NSCLC 成年患者被随机分配接受avelumab 10 mg/kg，每 2 周（Q2W），avelumab 10 mg/kg 每周一次（QW）治疗 12 周，然后 Q2W 或每 3 周接受铂类双联化疗。主要终点为独立审查委员会评估的总生存期（OS）和无进展生存期（PFS）。主要分析人群为高表达 PD-L1+肿瘤患者（≥80%的肿瘤细胞）。
结果
共 1214 例患者被随机分配至avelumab Q2W（n=366）、avelumab QW（n=322）或化疗（n=526）组。在主要分析人群中，avelumab Q2W（n=151）与化疗（n=216）相比，OS 和 PFS 的风险比（HR）分别为 0.85（95%置信区间[CI]：0.67-1.09；单侧 p=0.1032；中位 OS，20.1 与 14.9 个月）和 0.71（95% CI：0.54-0.93；单侧 p=0.0070；中位 PFS，8.4 与 5.6 个月）。avelumab QW（n=130）与化疗（n=129）相比，HR 分别为 0.79（95% CI：0.59-1.07；单侧 p=0.0630；中位 OS，19.3 与 15.3 个月）和 0.72（95% CI：0.52-0.98；单侧 p=0.0196；中位 PFS，7.5 与 5.6 个月）。未观察到新的安全性信号。
结论
avelumab 与铂类双联化疗相比，晚期 NSCLC 的中位 OS 和 PFS 更长，但 OS 和 PFS 的差异无统计学意义，试验未达到主要终点。
临床试验
gov 标识符：NCT02576574。
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