Sun Jingqi, Hao Junli, Li Xin, Xu Lu, Han Tao, Shi Sha, Li Heming, Zhao Mingfang
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning, China
J Immunother Cancer. 2025 Jun 22;13(6):e011622. doi: 10.1136/jitc-2025-011622.
In clinical practice, patients with non-small cell lung cancer (NSCLC) often receive low-dose programmed death-1 (PD-1) monoclonal antibodies due to physical or financial limitations. However, the efficacy and safety of low-dose compared with standard-dose PD-1 monoclonal antibodies remain underexplored.
This retrospective study included 400 patients with locally advanced or advanced NSCLC treated with PD-1 inhibitors as initial systemic therapy, either as monotherapy or combination therapy. Patients were classified into standard-dose (n=216), mid-treatment dose reduction (n=26), and low-dose (n=158) groups. Progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) were evaluated. Baseline characteristics were balanced using propensity score matching (PSM) in the combination therapy cohort. Non-inferiority of low-dose therapy for PFS (margin=1.3) and OS (margin=1.33) was based on clinical rationale and previous studies..
32 patients (8%) underwent surgery following systemic therapy. Among patients receiving first-line monotherapy (n=25), mPFS was 34.6 months for low-dose (L), 59.8 months for standard-dose (S), and 17.4 months for mid-treatment dose reduction (M), with no significant differences (HR (L vs S) = 0.81, 95% CI: 0.17 to 3.83; HR (M vs S) = 3.91, 95% CI: 0.45 to 34.14; p=0.37). In first-line combination therapy, before PSM, the mPFS was 16.8 vs 12.1 months and mOS was 35.7 vs 42.6 months (L vs S). After PSM, outcomes remained comparable (mPFS: 18.2 vs 11.2 months, p=0.22; mOS: 35.7 vs 28.7 months, p=0.47). Importantly, in the first-line combination therapy cohort, the incidence of grade ≥3 irAEs was significantly lower in the low-dose group (9.7% vs 17.9%, p=0.030). PFS met the non-inferiority criterion after PSM, whereas OS did not, likely due to an insufficient number of events.
Low-dose PD-1 monoclonal antibody therapy demonstrated comparable efficacy to standard-dose therapy with a lower incidence of severe irAEs in combination regimens. These findings suggest a cost-effective and safe alternative, warranting validation in future randomized controlled trials.
在临床实践中，非小细胞肺癌（NSCLC）患者常因身体或经济限制而接受低剂量程序性死亡受体1（PD-1）单克隆抗体治疗。然而，与标准剂量PD-1单克隆抗体相比，低剂量治疗的疗效和安全性仍未得到充分研究。
本回顾性研究纳入了400例接受PD-1抑制剂作为初始全身治疗的局部晚期或晚期NSCLC患者，治疗方式为单药治疗或联合治疗。患者被分为标准剂量组（n=216）、治疗中剂量减少组（n=26）和低剂量组（n=158）。评估无进展生存期（PFS）、总生存期（OS）和免疫相关不良事件（irAEs）。在联合治疗队列中，使用倾向评分匹配（PSM）使基线特征达到平衡。基于临床依据和既往研究，低剂量治疗在PFS（非劣效界值=1.3）和OS（非劣效界值=1.33）方面的非劣效性。
32例患者（8%）在全身治疗后接受了手术。在接受一线单药治疗的患者中（n=25），低剂量组（L）的中位PFS为34.6个月，标准剂量组（S）为59.8个月，治疗中剂量减少组（M）为17.4个月，差异无统计学意义（HR（L vs S）=0.81，95%CI：0.17至3.83；HR（M vs S）=3.91，95%CI：0.45至34.14；p=0.37）。在一线联合治疗中，PSM前，L组与S组的中位PFS分别为16.8个月和12.1个月，中位OS分别为35.7个月和42.6个月。PSM后，结果仍具有可比性（中位PFS：18.2个月 vs 11.2个月，p=0.22；中位OS：35.7个月 vs 28.7个月，p=0.47）。重要的是，在一线联合治疗队列中，低剂量组≥3级irAEs的发生率显著低于标准剂量组（9.7% vs 17.9%，p=0.030）。PSM后PFS符合非劣效性标准，而OS未达到，可能是由于事件数量不足。
低剂量PD-1单克隆抗体治疗在联合治疗方案中显示出与标准剂量治疗相当的疗效，且严重irAEs的发生率较低。这些发现提示了一种具有成本效益和安全性的替代方案，值得在未来的随机对照试验中进行验证。
