Pembrolizumab as first-line therapy for patients with PD-L1-positive advanced non-small cell lung cancer: a phase 1 trial
Pembrolizumab as first-line therapy for patients with PD-L1-positive advanced non-small cell lung cancer: a phase 1 trial
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DOI：
10.1093/annonc/mdx008
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发表时间：
2017-04-01
影响因子：
50.5
通讯作者：
Rizvi, N. A.
中科院分区：
文献类型：
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作者：
Hui, R.;Garon, E. B.;Rizvi, N. A.
背景：对于高度表达程序性死亡配体 1 (PD-L1) 的晚期非小细胞肺癌 (NSCLC) 患者，与化疗相比，派姆单抗作为一线和二线治疗可提高生存率。我们报告了派姆单抗作为晚期 NSCLC 患者一线治疗的长期安全性和临床活性，以及 PD-L1 表达和疗效之间的相关性。 患者和方法：在开放标签 1b 期 KEYNOTE-001 试验中，肿瘤表达 PD-L1（>= 1% 染色，使用原型测定评估）的初治晚期 NSCLC 患者被随机分配接受静脉注射派姆单抗，每次 2 或 10 mg/kg 3 (Q3W) 或 2 (Q2W) 周。每 9 周根据中心 RECIST v1.1 对所有接受 >= 1 剂量派姆单抗剂量的患者进行疗效评估。使用治疗前的肿瘤组织，临床检测将表达 PD-L1 的肿瘤细胞百分比量化为肿瘤比例评分 (TPS)。 结果：2013 年 3 月 1 日至 2015 年 9 月 18 日期间，101 名患者接受了帕博利珠单抗 2 mg/kg Q3W (n = 6)、10 mg/kg Q3W (n = 49) 或 10 mg/kg Q2W (n = 46)。其中，27 名 (26.7%) 的 TPS >= 50%，52 名 (51.5%) 的 TPS 1%-49%，12 名 (11.9%) 的 TPS= 50%，ORR、12 个月 PFS 和 12 个月 OS 较高 [14/27 (51.9%; 95% CI 32%-71%)、54%、和 85%] 分别高于总体人群 [27/101 (26.7%; 95% CI 18.4%-36.5%), 35%, 71%]。 Pembrolizumab 耐受性良好，只有 12 名 (11.9%) 患者经历了 3/4 级治疗相关不良事件，没有治疗相关死亡。结论：Pembrolizumab 为表达 PD-L1 的初治晚期 NSCLC 提供了有希望的长期 OS 益处，且安全性可控，在 TPS >= 50% 的患者中观察到最大疗效。
Background: Pembrolizumab improved survival as first-and second-line therapy compared with chemotherapy in patients with highly programmed death ligand 1 (PD-L1) expressing advanced non-small cell lung cancer (NSCLC). We report the long-term safety and clinical activity of pembrolizumab as first-line therapy for patients with advanced NSCLC and the correlation between PD-L1 expression and efficacy.Patients and methods: In the open-label phase 1b KEYNOTE-001 trial, treatment-naive patients with advanced NSCLC whose tumors expressed PD-L1 (>= 1% staining, assessed using a prototype assay) were randomly assigned to intravenous pembrolizumab 2 or 10 mg/kg every 3 (Q3W) or 2 (Q2W) weeks. Response was assessed per central RECIST v1.1 every 9 weeks in all patients who received >= 1 pembrolizumab dose. Using pre-treatment tumor tissue, a clinical assay quantified the percentage of tumor cells expressing PD-L1 as tumor proportion score (TPS).Results: Between 1 March 2013 and 18 September 2015, 101 patients received pembrolizumab 2 mg/kg Q3W (n = 6), 10 mg/kg Q3W (n = 49), or 10 mg/kg Q2W (n = 46). Of these, 27 (26.7%) had TPS >= 50%, 52 (51.5%) had TPS 1%-49%, and 12 (11.9%) had TPS= 50%, ORR, 12-month PFS, and 12-month OS were higher [14/27 (51.9%; 95% CI 32%-71%), 54%, and 85%, respectively] than the overall population [27/101 (26.7%; 95% CI 18.4%-36.5%), 35%, 71%]. Pembrolizumab was well tolerated, with only 12 (11.9%) patients experiencing grade 3/4 treatment-related adverse events and no treatment-related deaths.Conclusions: Pembrolizumab provides promising long-term OS benefit with a manageable safety profile for PD-L1-expressing treatment-naive advanced NSCLC, with greatest efficacy observed in patients with TPS >= 50%.