Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination.

Purpose: Effective treatments are needed for melanoma that progresses on inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1). We conducted the phase II LEAP-004 study to evaluate the combination of the multikinase inhibitor lenvatinib and the PD-1 inhibitor pembrolizumab in this population (ClinicalTrials.gov identifier: NCT03776136).

Lenvatinib dose, efficacy, and safety in the treatment of multiple malignancies.

Introduction: Lenvatinib is an oral multitargeted tyrosine kinase inhibitor that has shown efficacy and manageable safety across multiple cancer types. The recommended starting doses for lenvatinib differ across cancer types and indications based on whether it is used as monotherapy or as combination therapy.

Areas Covered: This review covers clinical trials that established the dosing paradigm and efficacy of lenvatinib and defined its adverse-event profile as a monotherapy; or in combination with the mTOR inhibitor, everolimus; or the anti-PD-1 antibody, pembrolizumab; and/or chemotherapy.

Assessing the Safety and Efficacy of Two Starting Doses of Lenvatinib Plus Everolimus in Patients with Renal Cell Carcinoma: A Randomized Phase 2 Trial.

Background: Lenvatinib (18 mg) plus everolimus (5 mg) is approved for patients with advanced renal cell carcinoma (RCC) after one or more prior antiangiogenic therapies.

Objective: To assess whether a lower starting dose of lenvatinib has comparable efficacy with improved tolerability for patients with advanced RCC treated with lenvatinib plus everolimus.

Design, Setting, And Participants: A randomized, open-label, phase 2 global trial was conducted in patients with advanced clear cell RCC and disease progression after one prior vascular endothelial growth factor-targeted therapy (prior anti-programmed death-1/programmed death ligand-1 therapy permitted).

Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer.

Background: Standard therapy for advanced endometrial cancer after failure of platinum-based chemotherapy remains unclear.

Methods: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen to receive either lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every 3 weeks) or chemotherapy of the treating physician's choice (doxorubicin at 60 mg per square meter of body-surface area, administered intravenously every 3 weeks, or paclitaxel at 80 mg per square meter, administered intravenously weekly [with a cycle of 3 weeks on and 1 week off]). The two primary end points were progression-free survival as assessed on blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.

Updating an empirical investigating risk perceptions associated with national ID cards in the wake of the global Covid-19 pandemic.

National ID cards have been debated for some time, especially with the recent Covid-19 global pandemic and increases in technological capabilities, coupled with the need for higher national security. This paper is an empirical extension of Smith's work but in light of the current economic and political turmoil. These differences were inspected from a gender perspective, but the distrust was generally universal.

Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (Study 111/KEYNOTE-146): a phase 1b/2 study.

Background: Despite advances in the first-line treatment of metastatic renal cell carcinoma (RCC), there is an unmet need for options to address disease progression during or after treatment with immune checkpoint inhibitors (ICIs). Pembrolizumab and lenvatinib are active as monotherapies in RCC; thus, we aimed to evaluate the combination of lenvatinib plus pembrolizumab in these patients.

Methods: We report results of the metastatic RCC cohort from an open-label phase 1b/2 study of lenvatinib plus pembrolizumab in patients aged at least 18 years with selected solid tumours and an Eastern Cooperative Oncology Group performance status of 0-1.

Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma.

Background: Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear.

Methods: In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment).

Significantly Minimizing Drug Wastage and the Cost of Cabazitaxel Used to Treat Metastatic Castration-Resistant Prostate Cancer.

Cabazitaxel is used to treat patients with metastatic castration-resistant prostate cancer progressing after docetaxel. It is prepackaged in 60 mg single-dose vials, a quantity much higher than the average prescribed dose, which leads to, substantial drug wastage (DW) and associated costs. To minimize DW we implemented a cost-saving, cohorting strategy where multiple patients scheduled to receive cabazitaxel (at a dose of 20mg/m every 3 wks) were cohorted and treated on a single weekday whenever possible.

The Utility of Serum CA9 for Prognostication in Prostate Cancer.

Background/aim: Carbonic anhydrase IX (CA9) catalyses the interconversion of carbon dioxide to carbonic acid and bicarbonate and is considered a putative biomarker of tumour hypoxia. We set out to evaluate the prognostic significance of CA9 in prostate cancer.

Patients And Methods: Plasma samples were assessed from 68 men with high-risk localised prostate cancer treated with radical prostatectomy (RP) or radiotherapy (RT), and 20 men with castration-resistant prostate cancer (CRPC) treated with docetaxel chemotherapy between 2010 and 2012 at the Princess Margaret Cancer Centre, Canada.

Drug discovery in advanced prostate cancer: translating biology into therapy.

Castration-resistant prostate cancer (CRPC) is associated with a poor prognosis and poses considerable therapeutic challenges. Recent genetic and technological advances have provided insights into prostate cancer biology and have enabled the identification of novel drug targets and potent molecularly targeted therapeutics for this disease. In this article, we review recent advances in prostate cancer target identification for drug discovery and discuss their promise and associated challenges.

Prostate-specific Antigen Decline After 4 Weeks of Treatment with Abiraterone Acetate and Overall Survival in Patients with Metastatic Castration-resistant Prostate Cancer.

Background: The availability of multiple new treatments for metastatic castration-resistant prostate cancer (mCRPC) mandates earlier treatment switches in the absence of a response. A decline in prostate-specific antigen (PSA) is widely used to monitor treatment response, but is not validated as an intermediate endpoint for overall survival (OS).

Objective: To evaluate the association between early PSA decline and OS following abiraterone acetate (AA) treatment.

Radar tracking and motion-sensitive cameras on flowers reveal the development of pollinator multi-destination routes over large spatial scales.

Central place foragers, such as pollinating bees, typically develop circuits (traplines) to visit multiple foraging sites in a manner that minimizes overall travel distance. Despite being taxonomically widespread, these routing behaviours remain poorly understood due to the difficulty of tracking the foraging history of animals in the wild. Here we examine how bumblebees (Bombus terrestris) develop and optimise traplines over large spatial scales by setting up an array of five artificial flowers arranged in a regular pentagon (50 m side length) and fitted with motion-sensitive video cameras to determine the sequence of visitation.

Operational effectiveness and quality assurance mechanisms with stochastic demand of blood supply: blood bank case study.

A general overview of various blood products operational effectiveness and related strategies that can be utilised by service providers (in particular, healthcare providers) is presented in the present study. In terms of the massive volumes of blood products, the North American blood centres collect more than eight million units of whole blood, which represents appropriately 50% of the US and Quebec, Canada?s volunteer donor blood supply. A case study of the quality inspection and inventory control concerns of the Central Blood Bank, located in the metropolitan area of Pittsburgh, PA, is presented.

Orientation cues for high-flying nocturnal insect migrants: do turbulence-induced temperature and velocity fluctuations indicate the mean wind flow?

Migratory insects flying at high altitude at night often show a degree of common alignment, sometimes with quite small angular dispersions around the mean. The observed orientation directions are often close to the downwind direction and this would seemingly be adaptive in that large insects could add their self-propelled speed to the wind speed, thus maximising their displacement in a given time. There are increasing indications that high-altitude orientation may be maintained by some intrinsic property of the wind rather than by visual perception of relative ground movement.

Gender preferences among electronic healthcare options: choices concerning neonatal care among professionals.

Technological advancements have migrated from personal-use electronics into the healthcare setting for security enhancements. Within maternity ward and nurseries, technology was seen as one of best way to protect newborns from abduction. Through hypothesis-testing and exploratory analysis, gender biases and extremely high levels of security were found within a web-enabled and professional sample of 200 respondents.

Flight metabolic rate and Pgi genotype influence butterfly dispersal rate in the field.

Dispersal is a key life-history trait, especially in species inhabiting fragmented landscapes. The process of dispersal is affected by a suite of morphological, physiological, and behavioral traits, all of which have a more or less complex genetic basis and are affected by the prevailing environmental conditions. To be able to identify genetic and phenotypic effects on dispersal, movements have to be recorded over relevant spatial and temporal scales.

Managing the quality of health information using electronic medical records: an exploratory study among clinical physicians.

As technology is advancing in the healthcare field, ways of reducing costs and improving quality are key initiatives in the tedious processes of operations planning. There are several ways of reducing costs and improving quality management. One such way is the implementation of Electronic Health Records (HERs).