Efficacy and safety of metronomic oral vinorelbine combined with PD-1 inhibitors as first-line therapy in advanced non-small-cell lung cancer in elderly patients.

8564 Background: Elderly individuals aged over 70 constitute the majority of Non-small cell lung cancer(NSCLC) patients. However, their poor general status, multiple co-morbidities, and limited social support present significant challenges in antitumor treatments, especially standard platinum-based chemotherapy. Metronomic chemotherapy (MCT) involves the regular administration of chemotherapy drugs at low doses, offering improved safety, anti-angiogenic tumor effects, and immune modulation compared to conventional chemotherapy. In light of these considerations, we have designed a phase II trial to evaluate the efficacy and safety of PD-1 inhibitors plus metronomic oral vinorelbine (mOV) as first-line therapy for elderly patients with metastatic NSCLC. Methods: Elderly patients(≥70 years) with previously untreated locally advanced or metastatic NSCLC without a sensitising EGFR mutation, ALK fusion or ROS1 fusion and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 were recruited for this study. Patients received PD-1 inhibitors combined with mOV (30mg, TIW1, day 1-3-5 per week) for 6 cycles, followed by PD-1 inhibitors maintenance until disease progression or intolerable toxicities. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles. Results: From March 2021 to November 2024, 37 patients were enrolled in the study. The median age was 77 with 31 (83.8%) males. Median follow-up time was 13.5 months (range 1.8 months-44.7 months). The median PFS was 10.9 months (95%Cl: 1.0 months-20.9 months) and the median OS was 26.2 months (95%Cl: (6.7 months-45.7 months). The ORR and DCR were 33.3% (95%C1: 17.3%-47.5%) and 86.1% (95%Cl: 71.9%-95.7%), respectively. Compared to those with low PD-L1 expression (PD-L1 TPS <50%), patients with high PD-L1 expression (PD-L1 TPS ≥50) had significant prolonged PFS [mPFS=6.1 months vs 23.0 months, p=0.01, HR = 0.19 (95%CI 0.05-0.69)] and OS [mOS=6.1 months vs not reached, p=0.02, HR = 0.09 (95%CI 0.01-0.70)]. Adverse events (AEs) of any grade were observed in 29 (78.4%) patients of which immune-related adverse events (irAEs) occurred in 14 (37.8%) patients. Grade 3-4 adverse reactions were reported in 5 (13.5%) patients, 4 of which were irAEs, including immune-associated pneumonia, myocarditis, myositis, enteritis and hepatitis. No grade 5 adverse events were reported. Conclusions: The regimen of PD-1 inhibitors plus mOV as first-line therapy showed significant survival benefits and a favorable safety profile in elderly patients with driver-gene-negative metastatic NSCLC, particularly those with high PD-L1 expression. Clinical trial information: ChiCTR2300074586 .