Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), member of the German Center for Lung Research (DZL), Grosshansdorf, Germany.
Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain.
J Clin Oncol. 2021 Jul 20;39(21):2339-2349. doi: 10.1200/JCO.21.00174. Epub 2021 Apr 19.
We report the first 5-year follow-up of any first-line phase III immunotherapy trial for non-small-cell lung cancer (NSCLC). KEYNOTE-024 (ClinicalTrials.gov identifier: NCT02142738) is an open-label, randomized controlled trial of pembrolizumab compared with platinum-based chemotherapy in patients with previously untreated NSCLC with a programmed death ligand-1 (PD-L1) tumor proportion score of at least 50% and no sensitizing or alterations. Previous analyses showed pembrolizumab significantly improved progression-free survival and overall survival (OS).
Eligible patients were randomly assigned (1:1) to pembrolizumab (200 mg once every 3 weeks for up to 35 cycles) or platinum-based chemotherapy. Patients in the chemotherapy group with progressive disease could cross over to pembrolizumab. The primary end point was progression-free survival; OS was a secondary end point.
Three hundred five patients were randomly assigned: 154 to pembrolizumab and 151 to chemotherapy. Median (range) time from randomization to data cutoff (June 1, 2020) was 59.9 (55.1-68.4) months. Among patients initially assigned to chemotherapy, 99 received subsequent anti-PD-1 or PD-L1 therapy, representing a 66.0% effective crossover rate. Median OS was 26.3 months (95% CI, 18.3 to 40.4) for pembrolizumab and 13.4 months (9.4-18.3) for chemotherapy (hazard ratio, 0.62; 95% CI, 0.48 to 0.81). Kaplan-Meier estimates of the 5-year OS rate were 31.9% for the pembrolizumab group and 16.3% for the chemotherapy group. Thirty-nine patients received 35 cycles (ie, approximately 2 years) of pembrolizumab, 82.1% of whom were still alive at data cutoff (approximately 5 years). Toxicity did not increase with longer treatment exposure.
Pembrolizumab provides a durable, clinically meaningful long-term OS benefit versus chemotherapy as first-line therapy for metastatic NSCLC with PD-L1 tumor proportion score of at least 50%.
我们报告了首个用于非小细胞肺癌（NSCLC）的一线 III 期免疫治疗试验的 5 年随访结果。KEYNOTE-024（ClinicalTrials.gov 标识符：NCT02142738）是一项开放标签、随机对照试验，比较了 pembrolizumab 与铂类化疗在未经治疗的 NSCLC 患者中的疗效，这些患者的程序性死亡配体 1（PD-L1）肿瘤比例评分至少为 50%，且无致敏或改变。先前的分析显示 pembrolizumab 显著改善了无进展生存期和总生存期（OS）。
符合条件的患者按 1:1 随机分配（1:1）接受 pembrolizumab（每 3 周 200mg，最多 35 个周期）或铂类化疗。化疗组中疾病进展的患者可以交叉使用 pembrolizumab。主要终点是无进展生存期；OS 是次要终点。
305 名患者被随机分配：154 名患者接受 pembrolizumab，151 名患者接受化疗。从随机分组到数据截止日期（2020 年 6 月 1 日）的中位（范围）时间为 59.9（55.1-68.4）个月。在最初被分配接受化疗的患者中，99 名患者接受了后续的抗 PD-1 或 PD-L1 治疗，有效交叉率为 66.0%。pembrolizumab 的中位 OS 为 26.3 个月（95%CI，18.3-40.4），化疗组为 13.4 个月（9.4-18.3）（风险比，0.62；95%CI，0.48-0.81）。Kaplan-Meier 估计 pembrolizumab 组的 5 年 OS 率为 31.9%，化疗组为 16.3%。39 名患者接受了 35 个周期（即大约 2 年）的 pembrolizumab 治疗，82.1%的患者在数据截止时（大约 5 年）仍存活。随着治疗时间的延长，毒性并未增加。
与化疗相比，在 PD-L1 肿瘤比例评分至少为 50%的转移性 NSCLC 患者中，pembrolizumab 作为一线治疗可提供持久的、有临床意义的长期 OS 获益。
