近日，南方医科大学吴一龙等研究人员合作完成在未经治疗的晚期非小细胞肺癌患者中PD-L1表达对信迪利单抗与帕博利珠单抗联合或不联合铂双联化疗的2期随机对照试验。相关论文于2023年12月26日在线发表在《科学通报》杂志上。

研究人员表示，在晚期非小细胞肺癌（NSCLC）患者的一线治疗中，尚未对不同的程序性细胞死亡-1（PD-1）抑制剂进行直接比较。使用PD-L1表达引导的免疫疗法的可行性仍然未知。

在这项开放标签的2期研究（NCT04252365）中，没有表皮生长因子受体（EGFR）或ALK改变的晚期NSCLC患者被随机（1:1）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%），或接受信迪利单抗或帕博利珠单抗加铂类化疗（PD-L1表达<50%）。样本量按最佳两阶段设计计算。主要终点是客观反应率（ORR）。该研究共纳入71名患者（信迪利单抗组，n=35；帕博利珠单抗组，n=36），达到了主要终点，信迪利单抗组的确诊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证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疗法的患者的确证ORR分别为54.5%（32.2%，75.6%）和45.4%（24.4%，67.8%）。

所有接受过信迪利单抗治疗的患者与所有接受过帕博利珠单抗治疗的患者的中位无进展生存期分别为6.9个月和8.1个月，其中单一疗法为7.6个月和11.0个月，联合疗法为7.4个月和7.1个月。所有接受信迪利单抗治疗的患者与所有接受帕博利珠单抗治疗的患者的中位总生存期分别为14.9个月与21.3个月，其中单一疗法为14.9个月与22.6个月，联合疗法为14.7个月与17.3个月。治疗相关不良事件与之前III期研究中单一疗法和联合疗法的安全性结果一致。不过，信迪利单抗的皮疹发生率高于帕博利珠单抗单药疗法。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2期研究。在晚期NSCLC患者中，无论PD-L1表达水平如何，信迪利单抗都具有良好的疗效和耐受性，其疗效和安全性与帕博利珠单抗相似。

附：英文原文

Title: 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

Author: anonymous

Issue&Volume: 2023/12/26

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.

DOI: 10.1016/j.scib.2023.12.046

Source: https://www.sciencedirect.com/science/article/pii/S2095927323009325