Different PD-L1 Assays Reveal Distinct Immunobiology and Clinical Outcomes in Urothelial Cancer.

Testing for PD-L1 expression by immunohistochemistry (IHC) is used to predict immune checkpoint blockade (ICB) benefit but has performed inconsistently in urothelial cancer (UC) clinical trials. Different approaches are used for PD-L1 IHC. We analyzed paired PD-L1 IHC data on UC samples using the SP142 and 22C3 assays from the phase 3 IMvigor130 trial and found discordant findings summarized by four phenotypes: PD-L1 positive by both assays (PD-L1 double positive; PD-L1DP), PD-L1 positive by the SP142 assay only (SP142 single positive; SP142SP), PD-L1 positive by the 22C3 assay only (22C3 single positive; 22C3SP), and PD-L1 negative by both assays double negative (PD-L1 double negative; PD-L1DN).

Understanding and Streamlining Dose Finding: From Dose Simulation to Dose Estimation.

Understanding drug dosing to fulfill safety and efficacy requirements in a patient population is an essential part of dose finding in clinical practice and drug development. The majority of current dose finding methods are simulation-based, which can be time consuming and resource intensive. Model-based simulations also do not guarantee that the dose, that will optimally fulfill the safety and efficacy endpoints, will be found.

A Personalized Approach for Oligometastatic Prostate Cancer: Current Understanding and Future Directions.

Oligometastatic prostate cancer (OMPC) represents an intermediate state in the progression from localized disease to widespread metastasis when the radiographically significant sites are limited in number and location. With no clear consensus on a definition, its diagnostic significance and associated optimal therapeutic approach remain controversial, posing a significant challenge for clinicians. The current standard of care for metastatic disease is to start systemic therapy; however, active surveillance and targeted radiotherapy have become attractive options to mitigate the long-term effects of androgen deprivation therapy (ADT).

Physiologically based Pharmacokinetic/Pharmacodynamic Modeling (PBPK/PD) of Famotidine in Pregnancy.

Famotidine, a H-receptor antagonist, is commonly used to treat heartburn and gastroesophageal reflux disease during pregnancy. However, information on the pharmacokinetics (PK) of famotidine in pregnant patients is limited since pregnant patients are usually excluded from clinical trials. This study aimed to develop and evaluate a physiologically based pharmacokinetic (PBPK) model for famotidine in non-pregnant and pregnant populations, and to combine it with a pharmacodynamic (PD) model to predict the effect of famotidine on intragastric pH.

Supplemental Intervention for Alcohol Use Disorder Treatment Patients With a Co-Occurring Anxiety Disorder: Technical Development and Functional Testing of an Autonomous Digital Program.

Background: Anxiety disorders are common in alcohol use disorder (AUD) treatment patients. Such co-occurring conditions ("comorbidity") have negative prognostic implications for AUD treatment outcomes, yet they commonly go unaddressed in standard AUD care. Over a decade ago, we developed and validated a cognitive behavioral therapy intervention to supplement standard AUD care that, when delivered by trained therapists, improves outcomes in comorbid patients.