Journal Article

Real-world effectiveness and safety of first-line chemoimmunotherapy combinations in metastatic non-small cell lung cancer with programmed death ligand-1 < 50%: results from an Italian observational study

Cristofano, Antonella, Delconte, Alessandro, Mazzi, Cristina, Lombardo, Fiorella, Colamartini, Francesca, Morgillo, Floriana, Verderame, Francesco, Marchetti, Fabiana, Galanti, Daniele, Savastano, Clementina, Gilli, Marina, Bria, Emilio, Veccia, Antonello, Vattemi, Emanuela, Corte, Carminia Maria Della, Occhipinti, Denis, Inno, Alessandro, Piscazzi, Daniele, Caffo, Orazio, Dessi, Alessandra, Genova, Carlo, Chiari, Rita, Busato, Simona, Bianco, Antonio, Kinspergher, Stefania, Pavan, Alberto, Vitiello, Fabiana, Sforza, Vincenzo, Palazzolo, Giovanni, Russano, Marco, Gori, Stefania, D’Argento, Ettore, Pizzutilo, Elio Gregory

2025

Overview

Introduction This multi-center, observational cohort study aimed to evaluate the real-world effectiveness and safety of two first-line chemoimmunotherapy combinations—pembrolizumab plus chemotherapy and nivolumab/ipilimumab plus chemotherapy—in patients with metastatic non-small cell lung cancer (NSCLC) and programmed death ligand-1 (PD-L1) expression < 50%. Patients and Methods The primary objectives were progression-free survival (PFS) and overall survival (OS) in the overall population. Secondary objectives included the incidence of chemotherapy-related and immune-related adverse events (irAEs). Results A total of 495 patients were enrolled, with 348 (70.3%) receiving pembrolizumab plus chemotherapy and 147 (29.7%) treated with nivolumab/ipilimumab plus chemotherapy. Overall, median follow-up was 11 (95% CI: 10.2 12.2) months. The median PFS was 10.9 months (95% CI: 9.6–13), and the median OS was 21.1 months (95% CI: 16.8–NR) in the overall population. In multivariable analysis, ECOG PS ≥ 2, PD-L1 expression < 1%, squamous histology, baseline steroid use, and the presence of CNS, bone, or liver metastases were significantly associated with shorter survival. No significant differences were observed between the pembrolizumab and nivolumab/ipilimumab cohorts in terms of PFS (11.83 vs. 9.83 months; HR 0.86, 95% CI: 0.67–1.11, p  = 0.3) or OS (21.3 vs. 20.6 months; HR 1.03, 95% CI: 0.76–1.39, p  = 0.9). Chemotherapy-related adverse events were more frequent in the pembrolizumab cohort, whereas irAEs were more common in the nivolumab/ipilimumab cohort. Conclusion In this real-world study, chemoimmunotherapy combinations demonstrated manageable toxicity profiles, with effectiveness comparable to that reported in pivotal phase 3 randomized trials. Pembrolizumab and nivolumab/ipilimumab showed similar real-world effectiveness but significantly different toxicity profiles.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V,Springer
• Subject: Adult / Adverse events / Aged / Aged, 80 and over / Antibodies, Monoclonal, Humanized - administration & dosage / Antibodies, Monoclonal, Humanized - therapeutic use / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Apoptosis / B7-H1 Antigen - metabolism / Cancer Research / Carcinoma, Non-Small-Cell Lung - drug therapy / Carcinoma, Non-Small-Cell Lung - immunology / Carcinoma, Non-Small-Cell Lung - metabolism / Carcinoma, Non-Small-Cell Lung - mortality / Carcinoma, Non-Small-Cell Lung - pathology / Chemotherapy / Chi-square test / Clinical trials / Enrollments / Female / Histology / Humans / Immunology / Immunotherapy / Immunotherapy - methods / Ipilimumab / Ipilimumab - administration & dosage / Italy / Ligands / Lung cancer / Lung Neoplasms - drug therapy / Lung Neoplasms - immunology / Lung Neoplasms - metabolism / Lung Neoplasms - mortality / Lung Neoplasms - pathology / Male / Mann-Whitney U test / Medical prognosis / Medicine / Medicine & Public Health / Metastases / Metastasis / Middle Aged / Mutation / Nivolumab / Nivolumab - administration & dosage / Non-small cell lung carcinoma / NSCLC / Observational studies / Oncology / PD-L1 / PD-L1 protein / Pembrolizumab / Performance evaluation / Small cell lung carcinoma / Toxicity