PD-L1 表达指导下信迪利单抗对比帕博利珠单抗联合或不联合铂类双药化疗用于未经治疗的晚期非小细胞肺癌患者（CTONG1901）：一项随机、对照、开放的 2 期临床研究。

PD-L1 expression guidance on sintilimab versus pembrolizumab with or without platinum-doublet chemotherapy in untreated patients with advanced non-small cell lung cancer (CTONG1901): A phase 2, randomized, controlled trial.

机构信息

Department of Hematology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China.

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.

出版信息

Sci Bull (Beijing). 2024 Feb 26;69(4):535-543. doi: 10.1016/j.scib.2023.12.046. Epub 2023 Dec 26.

DOI:10.1016/j.scib.2023.12.046

PMID:38185589

Abstract

No direct comparison has been performed between different programmed cell death-1 (PD-1) inhibitors for first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). The feasibility of using PD-L1-expression-guided immunotherapy remains unknown. In this open-label, phase 2 study (NCT04252365), patients with advanced NSCLC without EGFR or ALK alterations were randomized (1:1) to receive sintilimab or pembrolizumab monotherapy (PD-L1 expression ≥ 50%), or sintilimab or pembrolizumab plus platinum-based chemotherapy (PD-L1 expression < 50%). The sample size was calculated by optimal two-stage design. The primary endpoint was the objective response rate (ORR). The study included 71 patients (sintilimab arms, n = 35; pembrolizumab arms, n = 36) and met its primary endpoint, with a confirmed ORR of 51.4% (18/35) in the sintilimab arms. The confirmed ORR (95% confidence interval) was 46.2% (19.2%, 74.9%) and 42.9% (17.7%, 71.1%) for patients treated with sintilimab and pembrolizumab monotherapy; and 54.5% (32.2%, 75.6%) and 45.4% (24.4%, 67.8%) for those treated with sintilimab- and pembrolizumab-based combination therapies. The median progression-free survival was 6.9 versus 8.1 months for all sintilimab-treated versus all pembrolizumab-treated patients, respectively, in which it was 7.6 versus 11.0 months in monotherapy and 7.4 versus 7.1 months in combination therapies. The median overall survival was 14.9 versus 21.3 months for all sintilimab-treated versus all pembrolizumab-treated patients, respectively, in which it was 14.9 versus 22.6 months in monotherapy and 14.7 versus 17.3 months in combination therapies. Treatment-related adverse events were consistent with safety outcomes of monotherapy and combination therapy in previous phase III studies. However, the incidence of rash was higher with sintilimab than pembrolizumab monotherapy. This is the first prospective phase 2 study to directly compare two anti-PD-1 antibodies as first-line treatment in advanced NSCLC. Sintilimab was efficacious and well-tolerated irrespective of PD-L1 expression level in patients with advanced NSCLC and had similar efficacy and safety to pembrolizumab.

摘要

尚无研究比较不同的程序性死亡受体-1（PD-1）抑制剂用于晚期非小细胞肺癌（NSCLC）一线治疗。PD-L1 表达指导免疫治疗的可行性尚不清楚。在这项开放标签、Ⅱ期研究（NCT04252365）中，无 EGFR 或 ALK 改变的晚期 NSCLC 患者按 1:1 随机分配接受信迪利单抗或帕博利珠单抗单药治疗（PD-L1 表达≥50%）或信迪利单抗或帕博利珠单抗联合铂类化疗（PD-L1 表达<50%）。采用最优两阶段设计计算样本量。主要终点是客观缓解率（ORR）。该研究纳入 71 例患者（信迪利单抗组，n=35；帕博利珠单抗组，n=36），达到了主要终点，信迪利单抗组确认的 ORR 为 51.4%（18/35）。接受信迪利单抗和帕博利珠单抗单药治疗的患者的确认 ORR（95%置信区间）分别为 46.2%（19.2%，74.9%）和 42.9%（17.7%，71.1%），接受信迪利单抗和帕博利珠单抗联合治疗的患者为 54.5%（32.2%，75.6%）和 45.4%（24.4%，67.8%）。所有接受信迪利单抗治疗的患者中位无进展生存期为 6.9 个月，所有接受帕博利珠单抗治疗的患者为 8.1 个月，其中单药治疗分别为 7.6 个月和 11.0 个月，联合治疗分别为 7.4 个月和 7.1 个月。所有接受信迪利单抗治疗的患者中位总生存期为 14.9 个月，所有接受帕博利珠单抗治疗的患者为 21.3 个月，其中单药治疗分别为 14.9 个月和 22.6 个月，联合治疗分别为 14.7 个月和 17.3 个月。治疗相关不良事件与之前的Ⅲ期研究中单药和联合治疗的安全性结果一致。然而，与帕博利珠单抗单药治疗相比，信迪利单抗治疗的皮疹发生率更高。这是第一项直接比较两种抗 PD-1 抗体作为晚期 NSCLC 一线治疗的前瞻性Ⅱ期研究。信迪利单抗在晚期 NSCLC 患者中无论 PD-L1 表达水平如何均具有疗效且耐受性良好，与帕博利珠单抗的疗效和安全性相当。