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Results from the phase III Keynote-024 clinical trial established pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR , and ALK wild-type tumors. However, given the differences between patients treated in routine clinical practice and those treated in a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-ups, we designed an observational retrospective study of patients with metastatic NSCLC who were treated with pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were PFS and OS, determined using the Kaplan-Meier method. Response and safety were also evaluated. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression, and habitual smoking were prognostic factors for PFS, while age, sex, ECOG PS, habitual smoking and histology had an impact on OS. Multivariable analysis confirms the prognostic role of PD-L1 for PFS and of ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of pembrolizumab in the first-line setting, as well as a safety profile consistent with the results of Keynote-024 . Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be constructed as a potential conflict of interest.

Introduction: The phase III Keynote-189 trial established a first-line treatment combining pembrolizumab with pemetrexed and platinum as a standard treatment for patients with stage IV non-small cell lung cancer (NSCLC) without known EGFR and ALK driver mutations and independent of programmed cell death ligand 1 (PD-L1) expression. However, in Italy, eligibility for the National Health Service payment program is limited to patients with PD-L1 <50%. The PEMBROREAL study assesses the real-world effectiveness and safety of pembrolizumab in patients eligible for the National Health Service payment program., Methods: PEMBROREAL is a retrospective, observational study on patients with NSCLC who started pembrolizumab combined with pemetrexed and platinum within the reimbursability time window, considered as December 2019 to December 2020. The primary endpoints were to assess progression-free survival (PFS) and overall survival (OS; using the Kaplan-Meier method), response to therapy, and tolerability., Results: Until February 2022, 279 patients (median follow-up: 19.7 months) have been observed. The median PFS was 8.0 months (95% confidence interval: 6.5-9.2). OS was not reached, but we can estimate a 12- to 24-month survival rate for the combined treatment: 66.1% and 52.5%, respectively. PD-L1 expression and Eastern Cooperative Group (ECOG) Performance Status were both associated with PFS and OS. Overall, only 44.4% of patients reported an adverse event, whereas toxicity led to a 5.4% discontinuation rate., Conclusion: The results of the PEMBROREAL study have shown that the combined treatment of pembrolizumab with pemetrexed and platinum is effective for metastatic non-squamous NSCLC, even for patients with PD-L1 levels below 50%, despite the differences in patient demographics and pathological features compared to the Keynote-189 study. The adverse events reported during the study were more typical of chemotherapy treatment rather than immunotherapy, and physicians were able to manage them easily., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Cafaro, Foca, Nanni, Chiumente, Coppola, Baldo, Orzetti, Enrico, Ladisa, Lerose, Nardulli, Maiolino, Gradellini, Gasbarro, Carrucciu, Provasi, Cappelletto, Pasqualini, Vecchia, Veraldi, De Francesco, Crinò, Delmonte and Masini.)

Background: Non-small-cell lung carcinoma (NSCLC) accounts for 85-90% of all forms of lung cancer. Immuno-oncology represents a valid new approach but the high cost requires a specific evaluation of the health outcomes. This study describes the real-world efficacy, safety and cost profiles of the new anti-PD-1 immune-checkpoint inhibitors nivolumab and pembrolizumab on a cohort of 56 selected patients with advanced NSCLC., Methods: A retrospective, observational analysis was conducted on patients treated with immune checkpoint inhibitors from September 2015 to September 2018 at Azienda Ospedaliera Universitaria "Mater Domini" in Catanzaro, Italy. Data sources were medical records, internal prescription cards and reports of adverse reactions., Results: Fifty-six patients were diagnosed with advanced NSCLC, 64.3% characterized by a non-squamous histology, 30.3% squamous and 5.4% not specified. First-line treatment with pembrolizumab was administered to 11 patients for an average of 4.4 months, while 45 patients were treated with nivolumab for an average of 8.6 months. Data showed a survival rate of 95% after 6 months and 88% after 12 months. Most patients received immunotherapy as a second-line or subsequent treatment. In terms of prior therapy among all the patients, 43 had received platinum-based treatments. Indirect comparison with other real-world data studies showed variability in methodologies and an alignment in terms of results., Conclusion: This study, based on real-world data, was a first step in the assessment of the impact of the introduction of a significant new class of treatments, i.e. immunotherapy, and covers patients, treatments and outcomes, as well as organizational and economic variables.