Updated efficacy and safety of first-line PD-1 inhibitors plus metronomic oral vinorelbine in elderly patients with advanced NSCLC.

Abstract

e20590 Background: Elderly patients (≥70 years) with metastatic non-small cell lung cancer (NSCLC) face challenges with standard chemotherapy due to poor performance status, comorbidities, and limited social support. Metronomic chemotherapy (MCT), using low-dose continuous cytotoxic agents, shows promising safety and anti-angiogenic, immunomodulatory effects. This phase II study updates efficacy and safety of PD-1 inhibitors combined with metronomic oral vinorelbine (mOV) as first-line therapy in elderly metastatic NSCLC patients. Methods: Elderly patients (≥70 years) with untreated locally advanced or metastatic NSCLC, without EGFR mutations, ALK fusions, or ROS1 fusions, and ECOG performance status 0-1, received PD-1 inhibitors combined with mOV (30 mg, three times weekly on days 1, 3, and 5), followed by PD-1 inhibitor maintenance until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: From March 2021 to November 2025, 54 patients (median age 79 years, 79.6% male) were enrolled. After a median follow-up of 10.1 months, median PFS was 8.37 months (95% CI, 5.47–22.90) and median OS was 22.87 months (95% CI, 12.93–NR). The ORR was 25.9% (95% CI, 14.96%–39.65%) and DCR was 75.9% (95% CI, 62.36%–86.51%). Thirty-nine patients (72.2%) experienced at least one AE, with immune-related pneumonitis being the most frequent (18.5%). Grade 3–4 AEs occurred in 5 patients (9.3%), mainly immune-related pneumonitis, myocarditis, hepatitis, enteritis, and myositis, and bone marrow suppression. PD-L1-positive patients (TPS ≥1, 28 patients, 51.9%) had similar PFS (8.40 vs. 8.37 months) but significantly improved OS (30.17 months, 95% CI, 21.10–NR) compared to PD-L1-negative patients (20 patients, 37%), whose median OS was 13.13 months (95% CI, 8.60–NR). Patients with high PD-L1 expression (TPS ≥50%, 11 patients, 20.4%) showed the greatest benefit, with a median PFS of 25.83 months (95% CI, 20.30–NR) and a median OS not reached, along with ORR of 36.4%. Among patients aged ≥80 years (n = 22), median PFS was 8.97 months (95% CI, 3.53–NR) and median OS was 13.13 months (95% CI, 5.60–NR), with ORR of 18.2%. Sixteen patients (72.7%) experienced at least one AE, with grade 3-4 AEs observed in one patient (4.5%, myelosuppression). Conclusions: PD-1 inhibitors combined with mOV as first-line therapy provided significant survival benefits and acceptable tolerability in elderly patients with driver gene–negative metastatic NSCLC, particularly those with high PD-L1 expression. Similar efficacy and safety were observed in patients aged ≥80 years. Research Sponsor: National High-Level Hospital Clinical Research Funding (BJ-2023-073) and Beijing Medical Award Foundation Grant (YXJL-2020-0785-0251). Clinical trial information: ChiCTR2300074586;ChicTR21000 49487.