Lobaplatin-based chemotherapy with immunotherapy as first-line treatment in patients with advanced NSCLC: A real-world bidirectional cohort study.

Abstract

e20573 Background: Lobaplatin (LBP), a third-generation platinum-based antitumor drug, exhibits strong anti-cancer activity and low toxicity, without cross-resistance to cisplatin. Previous phase III studies have confirmed a similar efficacy of lobaplatin /paclitaxel regimen to that of cisplatin/paclitaxel for Chinese advanced NSCLC patients. We carried out a real-world study to evaluate the effectiveness and safety of LBP-based chemotherapy with immune checkpoint inhibitors (ICIs) as first-line treatment in driver-gene-negative advanced NSCLC population (ChiCTR2400079707). Methods: This observational bidirectional cohort study enrolled patients with driver-gene-negative advanced NSCLC who received first-line ICIs combined with LBP-based chemotherapy or carboplatin (CBP)-based chemotherapy. The primary endpoints were progression-free survival (PFS). Overall survival (OS) , objective response rate (ORR), disease control rate (DCR) and safety were also assessed. The efficacy of LBP or CBP combined with ICI tislelizumab was compared in 3D-bioprinted lung cancer patient-derived tissue (PDT) models. Results: From Jan 2019 to Dec 2023, a total of 203 patients were enrolled and evaluated, with 103 in LBP group and 100 in CBP group. Among them, 42.4% was adenocarcinoma and 44.8% was squamous cell carcinoma. At the data cutoff (Oct 10, 2024), the median follow-up time was 21.2 months. The median PFS was 14.0 months in LBP group and 13.0 months in CBP group. ORR and DCR in LBP group and CBP group were 47.6% vs. 58% (p=0.1368) and 92.2% vs. 96% (p=0.2552), respectively. The overall incidence of AEs and grade 3/4 AEs in LBP group and CBP group were 92.2 vs. 95.0% and 20.4% vs. 27.0%, respectively. The highest incidence of AEs were haematological toxicities. There was no treatment-related death in both groups. In 3D-bioprinted PDT models, LBP combined with tislelizumab achieved superior tumor suppression compared to the combination of CBP and tislelizumab, with lower IC50 values and reduced cell viability at Cmax concentrations. Both regimens showed similar effects on immune modulation, specifically in reducing CD279 (PD-1) expression on T cells. Conclusions: These findings suggest that the efficacy of lobaplatin was similar to carboplatin, and even safer when combined with ICIs in driver-gene-negative NSCLC. This study proposes a safer and feasible option for the first-line treatment for Chinese advanced NSCLC patients. Clinical trial information: ChiCTR2400079707 . Summary of AEs ≥10% of patients. Event LBP group CBP group Any Grade CTCAE≥Grade 3,% Any Grade CTCAE≥Grade 3,% Any AE 92.2 20.4 95.0 27.0 Leukopenia 49.5 10.7 55.0 12.0 Anemia 43.7 4.9 41.0 5.0 ALT increased 32.0 0.0 29.0 0.0 AST increased 28.2 0.0 31.0 1.0 Neutropenia 24.3 8.7 35.0 14.0 Thrombopenia 24.3 4.9 17.0 2.0 Nausea/Vomiting 11.7 0.0 22.0 1.0 Alkaline phosphatase increased 14.6 0.0 17.0 0.0 Pain 10.7 0.0 13.0 0.0