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.

The lack of head-to-head randomised trials and the consequences for patients and national health service: The case of non-small cell lung cancer.

INTRODUCTION: To introduce a drug to the market, it's not mandatory for it to be more effective and safer than the current treatment for the same condition. Consequently, head-to-head studies between the two best treatments for the same condition are not required, and this could result in a lack of information for patients, clinicians, and decision-makers. This study aims to evaluate the presence of head-to-head studies among the drugs used for the treatment of non-small cell lung cancer (NSCLC). METHODS: Taking into account the National Comprehensive Cancer Network (NCCN) guidelines updated to 2022, which list all available treatments for each NSCLC subtype, the search engine Pubmed and the platform clinicaltrials.gov were consulted to find all completed and ongoing head-to-head studies among various treatments for NSCLC. RESULTS: Among the anti-EGFR (epidermal growth factor receptor) drugs, 7 studies were found, with 6 completed and 5 registrational for drug commercialisation. No completed study to date has compared osimertinib and afatinib. For anti-ALK (anaplastic lymphoma kinase) drugs, 7 studies were found, with 5 completed. Alectinib, brigatinib, and lorlatinib have no completed comparison studies, but all were compared with crizotinib. Among various immunotherapy-based regimens, 5 studies were found, with only 1 completed. Therapeutic regimens based on pembrolizumab, atezolizumab, or the combination of nivolumab/ipilimumab have not been compared in studies published to date. CONCLUSION: There are few head-to-head studies comparing treatments for NSCLC; there are no such studies between the latest generation of drugs. Consequently, ambiguous areas exist due to the lack of comparative studies among the available evidence, preventing the clinician's choice of the most effective treatment and risking the patient receiving suboptimal therapy. Simultaneously, the price of the drug cannot be determined correctly, relying only on indirect evaluations from different trials. To dispel this uncertainty, it would be desirable to initiate a process that brings together the demands derived from clinical practice and clinical research to provide clinicians and patients with the best possible evidence.

Increasing pharmacy productivity and reducing medication turnaround times in an Italian comprehensive cancer center by implementing robotic chemotherapy drugs compounding.

INTRODUCTION: The management of antineoplastic drugs used for chemotherapy is widely recognized as a high-risk activity. In 2018, our oncology pharmacy implemented workflow improvements to manage the growing workload due to the centralisation of activities from a hospital's satellite pharmacy, moving towards automated compounding of antineoplastic drugs.The aim of this study was to determine the impact of the centralization on the productivity of the pharmacy department and evaluate the performances of the robotic chemotherapy drugs compounding. MATERIAL AND METHODS: Data were collected from the hospital information system and the workflow management software, and examined over a 3-year period (2017-2019). The total annual throughput in terms of doses prepared and patients treated and the Medication Turnaround Time (MTAT) were determined. Productivity and dosage accuracy were calculated for the robotic system. RESULTS: In 2018, the number of patients treated increased by 16.6%, consequently, the overall number of intravenous preparations compounded in the pharmacy increased by 17.2%. Regarding manual compounding, the total number of antineoplastic preparations decreased by about 2%. Investigational treatments manually compounded increased by about 27%, in contrast to the non-investigational treatments, which decreased by 9.4%. Regarding robotic compounding, the annual production increased by 50.4%. In 2018, the MTAT decreased about 24%. The dosage accuracy and precision of the total amount of doses were -1.1% and 1.2%, respectively. CONCLUSION: This study indicates that in the effort to satisfy an ever-increasing workload, computerization and automation are essential instruments to maintain and ensuring high standards of quality.

Cross-sectional database analysis of antidepressant prescribing in Italy.

Antidepressant drug trials have been criticised because they study atypical populations of depressive patients. The present cross-sectional database analysis was designed to define what constitutes a typical population of patients receiving antidepressants. From a database covering a population of 1,057,053 residents in Piedmont, Italy, and including all community (i.e. outside hospitals) prescriptions reimbursed by the National Health System, all prescriptions of antidepressant drugs dispensed during the first six months of 2000 were extracted. Using the general practice patient code all records were attributed to a sample of patients receiving antidepressants. During the study period 22,135 patients were dispensed one or more prescriptions, yielding a prevalence of use of 27.6 (CI 27.1, 28.0) per 1,000 females and 13.7 (CI 13.4, 14.0) per 1,000 males (female/male ratio 2.01). The prevalence of use progressively increased with age, with the highest rates in subjects over 75 years. The distribution of patients by number of antidepressant prescriptions showed that nearly 50% received only one or two prescriptions over the six months surveyed. Moreover, 18,676 subjects (84%) were prescribed antidepressants together with other medications. These data suggest shifting the focus of antidepressant drug trials from selected to non-selected populations of patients, including the elderly and patients with medical comorbidity, enrolled using entry criteria as close as possible to those adopted in everyday clinical practice. The high proportion of occasional antidepressant users suggests that clinical trials should follow all patients, without excluding those who fail to continue the study medication.