Real-World Safety and Outcome of First-Line Pembrolizumab Monotherapy for Metastatic NSCLC with PDL-1 Expression ≥ 50%: A National Italian Multicentric Cohort ("PEMBROREAL" Study).

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.

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).

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.

Susceptibility to COVID-19 in Patients Treated With Antimalarials: A Population-Based Study in Emilia-Romagna, Northern Italy.

OBJECTIVE: To evaluate the susceptibility to coronavirus disease 2019 (COVID-19) in patients with autoimmune conditions treated with antimalarials in a population-based study. METHODS: All residents treated with chloroquine (CQ)/hydroxychloroquine (HCQ) from July through December 2019 and living in 3 provinces of Regione Emilia-Romagna were identified by drug prescription registries and matched with the registry containing all residents living in the same areas who have had swabs and tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: A total of 4,408 patients were identified. The prevalence of patients receiving antimalarials was 0.85 per 1,000 men and 3.3 per 1,000 women. The cumulative incidence of testing during the study period was 2.7% in the general population and 3.8% among those receiving CQ or HCQ, while the cumulative incidence of testing positive was 0.55% in the general population and 0.70% among those receiving CQ/HCQ. Multivariate models showed that those receiving CQ/HCQ had a slightly higher probability of being tested compared to the general population (OR 1.09 [95% CI 0.94-1.28]), the same probability of being diagnosed as having COVID-19 (OR 0.94 [95% CI 0.66-1.34]), and a slightly lower probability of being positive once tested (OR 0.83 [95% CI 0.56-1.23]). None of the differences were significant. CONCLUSION: Our findings do not support the use of antimalarials as a prophylactic treatment of COVID-19.