Concomitant Medications Alter Clinical Outcomes in Patients with Advanced Digestive Tract Cancer Receiving PD-1 Checkpoint Inhibitors Combined with Antiangiogenetic Agents

Article

作者: Yang, Yanyan ; Wu, Zhiheng ; Han, Weidong ; Zheng, Yu ; Pan, Hongming ; Wang, Yiran ; Zhong, Xian ; Zhu, Xudong ; Tu, Jinming ; Yao, Junlin

PURPOSEOur study aimed to evaluate the impact of concomitant medications on the response and survival of patients with advanced digestive tract cancer receiving an immunotherapy-antiangiogenesis combination.METHODSWe conducted a three-center observational retrospective study of patients with advanced digestive tract cancer who received programmed death-1 (PD-1) inhibitors plus antiangiogenic agents between March 2019 and July 2022 in China. The patients had one of the three types of primary tumors: hepatocellular carcinoma (HCC), colorectal cancer (CRC), and gastric cancer (GC).RESULTSThe study included 352 patients. The most frequently prescribed co-medications were nonsteroidal anti-inflammatory drugs (NSAIDs) (46.3%), proton pump inhibitors (PPIs) (38.0%), systemic antibiotics (33.8%), and corticosteroids (30.1%). Probiotics had a direct correlation with a higher objective response rate (ORR) (OR 2.4, 95% CI 1.2 to 4.7, p = 0.013). Patients who received PPIs for gastritis/gastroesophageal reflux disease (GERD) (HR 0.7, 95% CI 0.5 to 1.0, p = 0.045), anticoagulants (HR 0.5, 95% CI 0.3 to 0.9, p = 0.009), and probiotics (HR 0.7, 95% CI 0.5 to 1.0, p = 0.034) had longer progression-free survival (PFS). Patients who received PPIs for gastritis/GERD (HR 0.6, 95% CI 0.4 to 0.9; p = 0.009) had longer overall survival (OS), while patients receiving opioids (HR 1.5, 95% CI 1.1 to 2.0, p = 0.010) had a significantly higher risk of death.CONCLUSIONPatients with advanced digestive tract cancer who were administered PPIs for gastritis/GERD indication, anticoagulants, or probiotics in combination with PD-1 inhibitors and antiangiogenic agents experienced improved clinical outcomes. However, opioid administration was linked to reduced OS in patients receiving combined therapy.

2022-04-03·Journal of Asthma4区 · 医学

Systemic glucocorticoid at discharge after hospitalization for pediatric asthma: a prospective pilot study

4区 · 医学

Article

作者: Sharma, Srish ; Wood, Julie K. ; Hanes, Holly C. ; Jones, Michael ; Eby Halvorson, Elizabeth ; McCalla, Chad D. ; Underdown, Mary Jane ; Woods, Elizabeth ; Duffin, Taylor Stukes ; Triplett, Andrea

OBJECTIVEWe examined asthma control in children hospitalized for status asthmaticus 7-10 days after discharge with or without an additional prescription for systemic corticosteroids.METHODSThis was a prospective observational study of patients aged 5-17 years with a documented history of asthma or β-agonist responsive wheezing admitted to the hospital for an acute asthma exacerbation. We compared patients who had any systemic corticosteroid prescribed at discharge with those who were not prescribed systemic corticosteroids at discharge. The primary outcomes were asthma control after discharge, as defined by the Asthma Control Test (ACT), and missed school days, which we modeled with multivariable linear and Poisson regression, respectively.RESULTSA total of 56 patients were included in the study, 29 (52%) received dexamethasone inpatient and then were discharged without additional prescribed systemic corticosteroids. Those without a corticosteroid prescription at discharge were less likely to have received noninvasive ventilation (p = 0.02), pulmonology consultation (p = 0.02), and continuous albuterol (p = 0.01) during hospitalization. These patients also tended toward shorter length of stay (p = 0.07) compared to those receiving systemic corticosteroid prescription at discharge. In multivariable models, being discharged without systemic corticosteroid prescription was associated with poorer asthma control after discharge [beta (95% CI), -2.21 (-2.65 to -1.77)] and more missed school days [coefficient estimate (95% CI), 0.87 (0.07-1.68)].CONCLUSIONSAfter hospitalization for an asthma exacerbation, patients not given systemic corticosteroids at discharge tended to have worse asthma control following discharge despite having less severe disease and requiring less aggressive inpatient management.Supplemental data for this article can be accessed at publisher's website.

2019-10-01·Targeted Oncology3区 · 医学

Evaluation of Clinically Relevant Drug–Drug Interactions and Population Pharmacokinetics of Darolutamide in Patients with Nonmetastatic Castration-Resistant Prostate Cancer: Results of Pre-Specified and Post Hoc Analyses of the Phase III ARAMIS Trial

3区 · 医学

Article

作者: Ploeger, Bart ; Shore, Neal ; Tammela, Teuvo L ; Prien, Olaf ; Zurth, Christian ; Kuss, Iris ; Smith, Matthew R ; Graudenz, Kristina ; Moss, Jonathan ; Fizazi, Karim ; Verholen, Frank ; Fricke, Robert ; Petrenciuc, Oana ; Koskinen, Mikko ; Gieschen, Hille ; Borghesi, Gustavo

BACKGROUNDDarolutamide, an androgen receptor antagonist with a distinct molecular structure, significantly prolonged metastasis-free survival versus placebo in the phase III ARAMIS study in men with nonmetastatic castration-resistant prostate cancer (nmCRPC). In this population, polypharmacy for age-related comorbidities is common and may increase drug-drug interaction (DDI) risks. Preclinical/phase I study data suggest darolutamide has a low DDI potential-other than breast cancer resistance protein/organic anion transporter protein substrates (e.g., statins), no clinically relevant effect on comedications is expected.OBJECTIVEOur objective was to evaluate the effect of commonly administered drugs on the pharmacokinetics of darolutamide and the effect of comedications potentially affected by darolutamide on safety in patients with nmCRPC.PATIENTS AND METHODSComorbidities and comedication use in the 1509 ARAMIS participants treated with darolutamide 600 mg twice daily or placebo were assessed. A population pharmacokinetic analysis evaluated whether comedications affected the pharmacokinetics of darolutamide in a subset of 388 patients. A subgroup analysis of adverse events (AEs) in statin users versus nonusers was conducted.RESULTSMost participants (median age 74 years) had at least one comorbidity (98.4% in both arms) and used at least one comedication (98.7% with darolutamide vs. 98.0% with placebo); these were similar across study arms. Despite frequent use of comedications with DDI potential, no significant effects on darolutamide pharmacokinetics were identified. Comedications included lipid-modifying agents (34.5%), β-blockers (29.7%), antithrombotics (42.8%), and systemic antibiotics (26.9%). AE incidence was similar across study arms in statin users and nonusers. Study limitations include the small sample size for sub-analyses.CONCLUSIONSThese analyses suggest the pharmacokinetic profile of darolutamide is not affected by a number of commonly administered drugs in patients with nmCRPC. Although pharmacokinetic data have indicated that darolutamide has the potential to interact with rosuvastatin, used to assess DDI in these studies, this finding did not seem to translate into increased AEs due to statin use in the ARAMIS trial. Clinicaltrials.gov identifier: NCT02200614.

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