Bronchial artery infusion of PD-1 inhibitors plus chemotherapy improves progression-free survival in advanced NSCLC: a prospective cohort study

Although PD-1/PD-L1 inhibitors have revolutionized advanced non-small cell lung cancer (NSCLC) treatment, systemic administration is limited by suboptimal local drug concentrations in tumors and the occurrence of immune-related adverse events (irAEs). This study aimed to evaluate the efficacy and safety of local administration of PD-1 inhibitors via bronchial artery infusion (BAI) for the treatment of NSCLC. This single-center prospective cohort study enrolled a total of 47 patients with advanced NSCLC (stage IIIB-IV) who were EGFR and ALK wild-type and exhibited poor response following 2 to 4 cycles of standard treatment. Patients were divided into BAI (n = 23) and Venous (n = 24) groups based on the route of PD-1 inhibitor administration. Both groups received PD-1 inhibitors combined with platinum-based chemotherapy. Notably, chemotherapy was administered via BAI in both groups, with the only difference being the route of PD-1 inhibitor delivery. The primary endpoints of the study was progression-free survival (PFS), and the secondary endpoints were objective response rates(ORR), disease control rates (DCR), overall survival (OS) and safety. At 6-month follow-up, higher ORR (47.8% vs. 16.7%, P = 0.026) and DCR were observed in the BAI group compared to the Venous group (73.9% vs. 41.6%, P = 0.014). The BAI cohort was associated with longer median PFS (11.1 vs. 6.6 months; HR = 0.372, 95% CI: 0.150-0.919; P = 0.030), with a trend toward improved OS (17.9 vs. 15.2 months, P = 0.085). Multivariable analysis identified BAI administration (HR = 0.372, P = 0.032) and younger age (HR = 2.838, P = 0.039) as independent predictors of prolonged PFS. No grade 3-4 treatment-related adverse events were observed in either group of patients. Immune-related pneumonitis (grade 1-2) occurred in 4.3% of patients in the BAI group and 4.2% in the venous group. Due to the limited sample size, a statistical comparison between groups was not performed. All adverse events were manageable with appropriate supportive treatment. BAI administration of PD-1 inhibitors was associated with improved therapeutic efficacy in advanced NSCLC, yielding longer PFS and higher ORR and DCR compared to the Venous group, without increasing severe toxicity.