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Observational Study
. 2025 Jul 12;74(8):266.
doi: 10.1007/s00262-025-04125-w.

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

Alessandro Inno  1 , Antonello Veccia  2 , Ettore D'Argento  3 , Floriana Morgillo  4 , Elio Gregory Pizzutilo  5 , Fabiana Vitiello  6 , Alberto Pavan  7 , Fiorella Lombardo  8 , Marco Russano  9 , Vincenzo Sforza  10 , Francesca Colamartini  11 , Carlo Genova  12   13 , Rita Chiari  14 , Antonella Cristofano  15 , Alessandro Delconte  16 , Emanuela Vattemi  17 , Alessandra Dessi  18 , Daniele Galanti  19 , Simona Busato  20 , Giovanni Palazzolo  21 , Clementina Savastano  22 , Antonio Bianco  23 , Francesco Verderame  24 , Cristina Mazzi  25 , Fabiana Marchetti  26 , Stefania Kinspergher  27 , Denis Occhipinti  3 , Carminia Maria Della Corte  4 , Daniele Piscazzi  5 , Marina Gilli  6 , Emilio Bria  3 , Orazio Caffo  27 , Stefania Gori  1
Affiliations
Observational Study

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

Alessandro Inno et al. Cancer Immunol Immunother. .

Abstract

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.

Keywords: Chemotherapy; Ipilimumab; NSCLC; Nivolumab; PD-L1; Pembrolizumab.

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Conflict of interest statement

Declarations. Conflict of interest: Alessandro Inno: honoraria/advisory board roles from Amgen, Astra Zeneca, Merck Sharp-Dome, Novartis, Roche. Carlo Genova: honoraria/advisory board roles from Amgen, Astra Zeneca, Bristol-Myers-Squibb, Daiichi-Sankyo, Eli Lilly, Merck-Sharp-Dohme, Novartis, Pierre Fabre, Regeneron, Roche, Takeda. The other authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
PFS (A) and OS (B) in the overall population. PFS: progression free survival. OS overall survival
Fig. 2
Fig. 2
PFS (A) and OS (B) in the two treatment cohorts. PFS progression free survival, OS overall survival. p value refers to the log-rank test
See this image and copyright information in PMC

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