TY - JOUR
T1 - Real-world effectiveness and safety of first-line chemoimmunotherapy combinations in metastatic non-small cell lung cancer with programmed death ligand-1
T2 - results from an Italian observational study
AU - Inno, Alessandro
AU - Veccia, Antonello
AU - D'Argento, Ettore
AU - Morgillo, Floriana
AU - Pizzutilo, Elio Gregory
AU - Vitiello, Fabiana
AU - Pavan, Alberto
AU - Lombardo, Fiorella
AU - Russano, Marco
AU - Sforza, Vincenzo
AU - Colamartini, Francesca
AU - Genova, Carlo
AU - Chiari, Rita
AU - Cristofano, Antonella
AU - Delconte, Alessandro
AU - Vattemi, Emanuela
AU - Dessi, Alessandra
AU - Galanti, Daniele
AU - Busato, Simona
AU - Palazzolo, Giovanni
AU - Savastano, Clementina
AU - Bianco, Antonio
AU - Verderame, Francesco
AU - Mazzi, Cristina
AU - Marchetti, Fabiana
AU - Kinspergher, Stefania
AU - Occhipinti, Denis
AU - Corte, Carminia Maria Della
AU - Piscazzi, Daniele
AU - Gilli, Marina
AU - Bria, Emilio
AU - Caffo, Orazio
AU - Gori, Stefania
N1 - Azienda Sanitaria Dell‘Alto Adige,
Bolzano, Italy
PY - 2025/7/12
Y1 - 2025/7/12
N2 - 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.
AB - 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.
KW - Humans
KW - Male
KW - Female
KW - Carcinoma, Non-Small-Cell Lung/drug therapy
KW - Middle Aged
KW - Lung Neoplasms/drug therapy
KW - Aged
KW - B7-H1 Antigen/metabolism
KW - Italy
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Antibodies, Monoclonal, Humanized/administration & dosage
KW - Adult
KW - Immunotherapy/methods
KW - Nivolumab/administration & dosage
KW - Aged, 80 and over
KW - Ipilimumab/administration & dosage
U2 - 10.1007/s00262-025-04125-w
DO - 10.1007/s00262-025-04125-w
M3 - Original Article
C2 - 40650694
SN - 0340-7004
VL - 74
SP - 266
JO - CANCER IMMUNOLOGY, IMMUNOTHERAPY : CII
JF - CANCER IMMUNOLOGY, IMMUNOTHERAPY : CII
IS - 8
M1 - 266
ER -