A real-world study on the efficacy and safety of low-dose PD-1 monoclonal antibody alone or in combination as the first-line treatment for advanced non-small cell lung cancer.

Background: 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.

Methods: 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..

Results: 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.

Conclusions: 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.