AUTHOR=Cafaro Alessandro , Foca Flavia , Nanni Oriana , Chiumente Marco , Coppola Marina , Baldo Paolo , Orzetti Sabrina , Enrico Fiorenza , Ladisa Vito , Lerose Rosa , Nardulli Patrizia , Maiolino Piera , Gradellini Federica , Gasbarro Anna Rita , Carrucciu Gisella , Provasi Riccardo , Cappelletto Paola Cristina , Pasqualini Alessandra , Vecchia Stefano , Veraldi Marianna , De Francesco Adele Emanuela , Crinò Lucio , Delmonte Angelo , Masini Carla TITLE=A real-world retrospective, observational study of first-line pembrolizumab plus chemotherapy for metastatic non-squamous non-small cell lung cancer with PD-L1 tumor proportion score < 50% (PEMBROREAL) JOURNAL=Frontiers in Oncology VOLUME=Volume 14 - 2024 YEAR=2024 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1351995 DOI=10.3389/fonc.2024.1351995 ISSN=2234-943X ABSTRACT=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.