Efficacy and Safety of First-line Pembrolizumab Plus Platinum and Pemetrexed in Elderly Patients with Non-squamous Non-small-cell Lung Cancer

Intern Med. 2025 Jan 1;64(1):55-64. doi: 10.2169/internalmedicine.3649-24. Epub 2024 May 16.

Abstract

Objective Pembrolizumab plus platinum and pemetrexed (Pemb-Plt-PEM) combination therapy is an effective first-line treatment for advanced non-squamous non-small-cell lung cancer (NSCLC), regardless of programmed death-ligand 1 expression. However, the effectiveness and feasibility of first-line Pemb-Plt-PEM therapy in elderly patients (≥75 years old) remain unclear. Therefore, this study investigated the safety and efficacy of first-line Pemb-Plt-PEM in elderly patients with non-squamous NSCLC. Methods We retrospectively evaluated the data of patients ≥75 years old with non-squamous NSCLC who were treated with first-line Pemb-Plt-PEM from December 2018 to December 2020 at 10 institutes in Japan. Data on patient characteristics, efficacy of Pemb-Plt-PEM therapy, and the type and severity of adverse events were reviewed. Results Thirty patients [20 men and 10 women; median age: 76 (range: 75-82) years old] were included in the analysis. The overall response rate, disease control rate, median progression-free survival (PFS), and median overall survival (OS) were 40.0%, 66.7%, 7.5 and 24.0 months, respectively. The treatment-related deaths were caused by pneumonitis. First-line Pemb-Plt-PEM was associated with the PFS, based on the neutrophil-to-lymphocyte ratio (NLR). The PFS for low and high NLR values was 10.1 and 2.0 months, respectively. Furthermore, the sex and NLR influenced the association between Pemb-Plt-PEM and the OS. The OS for low and high NLR values was 32.8 and 2.6 months, respectively. Conclusion First-line Pemb-Plt-PEM therapy is effective and feasible in elderly patients with non-squamous NSCLC.

Keywords: PD-L1; advanced non-squamous non-small cell lung cancer; elderly patients; first-line chemotherapy; pembrolizumab; pemetrexed.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Female
  • Humans
  • Japan
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Pemetrexed* / administration & dosage
  • Pemetrexed* / adverse effects
  • Pemetrexed* / therapeutic use
  • Progression-Free Survival
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Pemetrexed
  • pembrolizumab
  • Antibodies, Monoclonal, Humanized