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.

[Phosphate containing enemas: one undervalued risky practice? The management of an adverse event]. / Gli enteroclismi a base di fosfati: una pratica rischiosa sottovalutata? La gestione di un evento avverso.

INTRODUCTION: The phosphate-containing enemas are widely used, both to manage constipation and as a preparation for endoscopic procedures and surgery in adults and children. Many studies report that the use of these laxatives can be dangerous. OBJECTIVE: To identify possible prevention strategies starting from a severe adverse reaction due to repeated administrations of phosphate enemas. METHODS: A working group was started, the literature was reviewed and recommendations for an appropriate use of enemas were discussed and implemented, to improve patients' safety. RESULTS: Phosphate-containing enemas were replaced with 125 ml water enemas; recommendations were spread to strongly limit the use of phosphate containing enemas and the use of laxative in the first and second semester of 2012, were confronted showing a change in habits and a reduction in the use of phosphate containing enemas. CONCLUSIONS: The implementation of several strategies, originated from an adverse event, succeeded in modifying the use of laxatives and phosphate-containing enemas.