Abstract LB197: Efficacy, safety, and protein markers of PD-1 inhibitors plus metronomic oral vinorelbine in elderly metastatic non-small-cell lung cancer patients
Authors: Yue Yuan, Yumeng Tian, Qian Wei, Xin Nie, Junling Ma, Lin Li
Journal: Cancer Research (2025)

Abstract Background: The treatment of non-small cell lung cancer (NSCLC) lacking driver oncogenes remains a formidable challenge, particularly in cases where resistance to programmed cell death protein 1/programmed death-ligand 1 (PD-(L)1) blockade has been acquired. Metronomic chemotherapy (MCT), which involves the frequent administration of chemotherapy drugs at reduced doses, offers a more favorable safety profile, anti-tumor angiogenesis, and immune modulatory effects compared to conventional chemotherapy. In this study, we conducted a retrospective analysis to assess the efficacy and safety of combining PD-1 inhibitors with metronomic oral vinorelbine (mOV) in patients with pre-treated metastatic NSCLC. Additionally, we identified protein markers associated with this novel treatment approach through plasma proteomics testing. Methods: Patients with histologically or cytologically confirmed unresectable stage III and IV NSCLC and received at least one systematic treatment. Pts received PD-1 inhibitors combined with mOV (30mg, TIW1, day 1-3-5 per week) until disease progression or intolerable side effects. The primary endpoint was progression-free survival (PFS). Peripheral plasma was collected from 10 patients at the beginning and early stages of treatment (1-3 stages after treatment) and were analyzed using the SOMAscan Assay Kit for human serum, which measures the expression of 11000 types of human proteins using highly selective single-stranded modified Slow Off-rate Modified DNA Aptamers (SOMAmer). Results: From May 2020 to June 2023, 23 pts were evaluated for inclusion in the study. The median age was 70(range: 48-85) with 18(78%) males. Median follow-up was 35.6 months (range 27.2months-44.13months), and the median PFS was 5.63 months (95%Cl: 4.03-16.5 months). The median OS was 24.8 months (95%Cl: (13.5 months-NA). The ORR and DCR were 13% (95%C1: 1.44%-27.6%) and 69.6% (95%Cl: 49.2%-89.9%), respectively. Adverse events (AEs)with any grade were observed in 20(86.9%) pts, of which grade III-IV AEs were observed in 4 (17.4%) pts. Immune-related adverse events (irAEs) occurred in 4 (17.4%) pts, of which grade III-IV irAEs occurred in 2 (8.7%) patients with G3 interstitial pneumonia. According to the length of PFS, patients were divided into a good efficacy group and a poor efficacy group. Baseline differential protein analysis identified 321 differential proteins, and pathway enrichment results showed that they were mainly enriched in the JAK-STAT signaling pathway, AMPK signaling pathway, PI3K Akt signaling pathway, PD-1 checkpoint pathway, and other pathways. The differential protein analysis before and after treatment identified SH2D2A and HOMER3, two proteins involved in T-cell activation. The levels of these two proteins were lower in the good efficacy group before treatment and increased after treatment, while they showed the opposite trend in the poor efficacy group. Conclusions: The combination of PD-1 inhibitors plus mOV has good efficacy and safety in the postoperative treatment of elderly patients. Protein biomarkers can help accurately identify the patients that will benefit from this treatment regimen. Research Sponsor: National High Level Hospital Clinical Research Funding (BJ-2023-073) Citation Format: Yue Yuan, Yumeng Tian, Qian Wei, Xin Nie, Junling Ma, Lin Li. Efficacy, safety, and protein markers of PD-1 inhibitors plus metronomic oral vinorelbine in elderly metastatic non-small-cell lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB197.