Real-world evidence of sorafenib for the treatment of hepatocellular carcinoma: A single-center study.

Context: Hepatocellular carcinoma is the third leading cause of cancer death. Currently, sorafenib is the treatment of choice in advanced hepatocarcinoma. Aims: Assessing the effectiveness and toxicity of sorafenib in real-word clinical practice in patients with hepatocarcinoma. Settings and Design: Single-centered observational retrospective study. Methods and Material: We included patients with hepatocarcinoma who began treatment with sorafenib between 2008 and 2018. We evaluated overall survival, time to progression, and response using RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events version 5. 2020. Statistical Analysis Used: Kaplan-Meier curves and the log-rank test were used to determine the survival time and estimate factors associated with these events. Data were analyzed with SPSS 19.0 software. Results: We included 36 patients (88.9% male) with an average age of 64 ± 3.4 years. The tumor stage was advanced (C) in 21 patients (61.8%). We obtained a median overall survival of 8.5 months (IQR 3.14-18.9) and a time to progression of 4.5 months (IQR 2.4-8.8). The main degree of response was progression in 19 patients (36.1%), followed by stable disease in 13 (52.8%). The most commonly reported adverse reactions were: constitutional (83.3%), gastrointestinal (55%) and dermatological symptoms (50.0%). The development of grades 3 or 4 toxicity was not associated with increased overall survival (P = 0.719). Conclusions: The findings of the survival analysis obtained in real practice are similar to those obtained in pivotal clinical trials. Adverse reactions were different from those expected.

Regorafenib and trifluridine/tipiracil in real clinical practice.

Background: Colorectal cancer is the ninth leading cause of death in Spain. The latest therapeutic developments in the advanced stages of this disease are the oral drugs trifluridine/tipiracil and regorafenib. Objective: Results of clinical trials (CTs) are not in real conditions and therefore, we want to study the effectiveness and the safety profile in the usual clinical practice and compare it with the bibliography. Materials and Methods: A retrospective and unicentric study was carried out in a health area of 500,000 inhabitants. Patients who started treatment with regorafenib and/or trifluridine/tipiracil were included from the date of marketing until June 2019. Patient-related variables, pathology, effectiveness, and treatment toxicity were collected. The statistical analysis was carried out with the PSPP program. Results: Fifty-four patients were analyzed. Men accounted for 59.3% of patients. Regorafenib was the treatment for 22.2% of patients and 77.8% received trifluridine/tipiracil. The reason for the drug's suspension was the disease progression in 85.2% of patients. No patient had a full response and 3.2% achieved partial response. The median progression-free survival time in treatments with regorafenib was 2.5 months (95% confidence interval [CI]: 0.0-5.4) and the overall survival time was 3.1 months (95% CI: 0.0-6.7), while in treatments with trifluridine/tipiracil, these data were, respectively, 2.8 (95% CI: 2.5-3.2) and 5.7 months (95% CI: 3.8-7.6). Side effects occurred in 91.7% of patients treated with regorafenib and in 100% of treated with trifluridine/tipiracil. Hematological adverse reactions were, on average, 0.4 ± 0.5/patient with regorafenib and 1.5 ± 0.9 with trifluridine/tipiracil. General (77.8%) and gastrointestinal disorders (50%) were common with both drugs. Conclusions: The effectiveness results of standard clinical practice are lower than those described in CTs and in the literature. The toxicity profile does reproduce what is described in the bibliography.

Real-world prevalence and consequences of potential drug-drug interactions in the first-wave COVID-19 treatments.

WHAT IS KNOWN AND OBJECTIVE: Initial treatment recommendations of COVID-19 were based on the use of antimicrobial drugs and immunomodulators. Although information on drug interactions was available for other pathologies, there was little evidence in the treatment of COVID-19. The objective of this study was to analyse the potential drug-drug interactions (pDDIs) derived from the medication used in COVID-19 patients in the first pandemic wave and to evaluate the real consequences of such interactions in clinical practice. METHODS: Cohort, retrospective and single-centre study carried out in a third-level hospital. Adult patients, admitted with suspected COVID-19, that received at least one dose of hydroxychloroquine, lopinavir/ritonavir, interferon beta 1-b or tocilizumab and with any pDDIs according to "Liverpool Drug Interaction Group" between March and May 2020 were included. The possible consequences of pDDIs at the QTc interval level or any other adverse event according to the patient's medical record were analysed. A descriptive analysis was carried out to assess possible factors that may affect the QTc interval prolongation. RESULTS AND DISCUSSION: Two hundred and eighteen (62.3%) patients of a total of 350 patients admitted with COVID-19 had at least one pDDI. There were 598 pDDIs. Thirty-eight pDDIs (6.3%) were categorized as not recommended or contraindicated. The mean value difference between baseline and pDDI posterior ECG was 412.3 ms ± 25.8 ms vs. 426.3 ms ± 26.7 ms; p < 0.001. Seven patients (5.7%) had a clinically significant alteration of QTc. A total of 44 non-cardiological events (7.3%) with a possible connection to a pDDI were detected. WHAT IS NEW AND CONCLUSION: The number of pDDIs in patients admitted for COVID-19 in the first pandemic wave was remarkably high. However, clinical consequences occurred in a low percentage of patients. Interactions involving medications that would be contraindicated for concomitant administration are rare. Knowledge of these pDDIs and their consequences could help to establish appropriate therapeutic strategies in patients with COVID-19 or other diseases with these treatments.