Castlebrook Clinical Trials Digest — 2026-W15

Vulsteke C et al. · N Engl J Med. 2026 Apr 2;394(13):1257-1269. doi: 10.1056/NEJMoa2511674. Epub · PMID 41707170
Why it matters: Published in N Engl J Med, this Phase 3 Trial contributes pivotal evidence in Oncology with direct implications for clinical practice.
Author information: Integrated Cancer Center Ghent, AZ Maria Middelares, Ghent, Belgium. Center for Oncologic Research, Antwerp University, Antwerp, Belgium.

Rosen CJ et al. · N Engl J Med. 2026 Apr 2;394(13):1313-1324. doi: 10.1056/NEJMra2500106. · PMID 41931049
Why it matters: Published in N Engl J Med, this Other contributes pivotal evidence in Endocrinology & Metabolism with direct implications for clinical practice.
Glucagon-like peptide-1 (GLP-1) receptor agonists are incretin analogues that promote glucose-mediated insulin release and are used to treat type 2 diabetes mellitus and obesity. GLP-1 receptor agonists and GLP-1 and glucose-dependent insulinotropic peptide agonists have several mechanisms of action, including reduction of gastric emptying, inhibition of glucagon secretion, beneficial changes in the intestinal microbiome, and direct effects on hypothalamic nuclei to enhance satiety (which promotes weight loss). Beyond the impressive effects of GLP-1 receptor agonists on blood glucose levels and body weight, large-scale randomized, controlled trials have shown that GLP-1 receptor agonists reduce cardiovascular risk and slow progression to renal failure in persons at high risk and those with type 2 diabetes.

Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation. · N Engl J Med, 2026 · PMID 41849741

Apolipoprotein E Mimetic Peptide CN-105 and Postoperative Delirium in Older
Patients: The Phase 2 MARBLE Randomized Clinical Trial. · JAMA Netw Open, 2026 · PMID 41931297

Discontinuation of Beta-Blocker Therapy after Myocardial Infarction. · N Engl J Med, 2026 · PMID 41910427

Pharmacotherapy for mild hypertension. · Cochrane Database Syst Rev, 2026 · PMID 41925078

Two-Year Outcomes of Less Invasive Surfactant Administration Among Preterm
Neonates: A Secondary Analysis of a Randomized Clinical Trial. · JAMA Netw Open, 2026 · PMID 41915392

GLP-1 Receptor Agonists.
Rosen CJ et al. · N Engl J Med. 2026 Apr 2;394(13):1313-1324. doi: 10.1056/NEJMra2500106. · PMID 41931049

GLP-1 Receptor Agonists and Noncardiometabolic Outcomes: An Umbrella Review of
Meta-Analyses. · JAMA Netw Open, 2026 · PMID 41915388

Intravenous immunoglobulin treatment for long COVID: a case report of clinical
and immunological findings. · Lancet Infect Dis, 2026 · PMID 41932347

Target product profiles for treatments to delay or prevent symptomatic
Alzheimer's disease. · Nat Med, 2026 · PMID 41933174

Melatonin treatment for neonatal encephalopathy. · Cochrane Database Syst Rev, 2026 · PMID 41925053

Lysosomal homeostasis at the crossroads of neurodegeneration. · J Clin Invest, 2026 · PMID 41919495

Higher drinking frequency corresponds to lower synaptic density in people with
alcohol use disorder. · J Clin Invest, 2026 · PMID 41528802

Switch to single-tablet bictegravir-lenacapavir from a complex HIV regimen
(ARTISTRY-1): a randomised, open-label, phase 3 clinical trial. · Lancet, 2026 · PMID 41763229

Anti-infective vaccination strategies in patients with haematological
malignancies or solid tumours: updated guideline of the Infectious Diseases
Working Party of the German Society for Hematology and Medical Oncology. · Lancet Oncol, 2026 · PMID 41926972

Retroperitoneal fibrosis. · Lancet, 2026 · PMID 41905382

Sepsis. · Lancet, 2026 · PMID 41765030

Lenacapavir as pre-exposure prophylaxis for HIV prevention. · Cochrane Database Syst Rev, 2026 · PMID 41919720

Targeting neutrophil extracellular traps in liver ischemia-reperfusion injury:
From molecular mechanisms to pharmacological and translational opportunities. · Biomed Pharmacother, 2026 · PMID 41934899

Genetic analysis of neurodegenerative diseases. · J Clin Invest, 2026 · PMID 41919497

Plasma chondroitin sulfate predicts the effectiveness of fluid resuscitation
strategies in patients with sepsis. · J Clin Invest, 2026 · PMID 41632536

Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer.
Vulsteke C et al. · N Engl J Med. 2026 Apr 2;394(13):1257-1269. doi: 10.1056/NEJMoa2511674. Epub · PMID 41707170

Deep learning on histopathological images to predict breast cancer recurrence
risk and chemotherapy benefit: a multicentre, model development and validation
study. · Lancet Oncol, 2026 · PMID 41831466

Fulzerasib plus cetuximab in first-line KRAS(G12C)-mutated non-small-cell lung
cancer (KROCUS): a single-arm, multicentre, phase 1b/2 trial. · Lancet Oncol, 2026 · PMID 41926959

Benmelstobart plus anlotinib versus pembrolizumab as first-line treatment for
PD-L1-positive, advanced non-small-cell lung cancer (CAMPASS): a blinded,
randomised, controlled, phase 3 trial. · Lancet Oncol, 2026 · PMID 41825453

Assessment of survival benefit from sentinel node biopsy for melanoma: a
systematic review and meta-analysis. · Lancet Oncol, 2026 · PMID 41796592

Proton beam therapy for oropharyngeal cancer (TORPEdO): a phase 3, randomised controlled trial. · Lancet, 2026 · PMID 41875914

Medial retropharyngeal nodal region sparing radiotherapy in nasopharyngeal
carcinoma: five year analysis of open label, non-inferiority, multicentre,
randomised phase 3 trial. · BMJ, 2026 · PMID 41916649

CRISPR-Cas12a Gene Editing of HBG1 and HBG2 Promoters to Treat β-Thalassemia. · N Engl J Med, 2026 · PMID 41931048

Advancing cancer equity in seven high-income countries: an analysis of policy
levers and National Cancer Control Plans. · Lancet Oncol, 2026 · PMID 41926973

Ifinatamab deruxtecan, a B7-H3-directed antibody-drug conjugate, in patients
with advanced solid tumours (IDeate-PanTumor01): dose-escalation results from a phase 1/2 trial. · Lancet Oncol, 2026 · PMID 41926962

[(177)Lu]Lu-PSMA-617 in combination with pembrolizumab for treatment of
metastatic castration resistant prostate cancer (PRINCE): a single-arm, phase
1b/2 study. · Lancet Oncol, 2026 · PMID 41926961

[(177)Lu]-PSMA-617-PSMA-617 in oligometastatic hormone sensitive prostate cancer
(BULLSEYE): an open-label, randomised, phase 2 study. · Lancet Oncol, 2026 · PMID 41926960

A practical toolkit with recommendations for analysing and visualising
patient-reported outcomes in early phase dose-finding oncology trials
(OPTIMISE-AR). · Lancet Oncol, 2026 · PMID 41861833

Neoadjuvant sacituzumab govitecan plus pembrolizumab, followed by adjuvant
pembrolizumab, in patients with muscle-invasive bladder cancer (SURE-02): a
single-arm, phase 2 study. · Lancet Oncol, 2026 · PMID 41771275

Significant Incidental Findings in the National Lung Screening Trial and
Diagnosis of Extrapulmonary Cancer. · JAMA Netw Open, 2026 · PMID 41915394

Radiofrequency Ablation and Chemotherapy vs Chemotherapy Only in Locally
Advanced Pancreatic Cancer: The PELICAN Randomized Clinical Trial. · JAMA Netw Open, 2026 · PMID 41915391

Exosomal PD-L1 in hepatocellular carcinoma: Immune evasion mechanisms,
diagnostic value, and strategies for therapeutic targeting. · Biomed Pharmacother, 2026 · PMID 41904892

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) for preventing
colorectal cancer and colorectal adenoma in the general population. · Cochrane Database Syst Rev, 2026 · PMID 41919561

Aptamers in cancer therapy: Why has clinical translation lagged behind
preclinical promise? · Biomed Pharmacother, 2026 · PMID 41931849

Leukemic stem cells as drivers of therapeutic resistance in acute myeloid
leukemia. · Biomed Pharmacother, 2026 · PMID 41922112

Cancer cell migration under control of human cathelicidin LL-37. · Biomed Pharmacother, 2026 · PMID 41916132

CRISPR-Cas12a Gene Editing of HBG1 and HBG2 Promoters to Treat Sickle Cell
Disease. · N Engl J Med, 2026 · PMID 41931047

Autosomal dominant polycystic kidney disease. · Lancet, 2026 · PMID 41771281

Principles of cytoreductive surgery for primary and metastatic peritoneal
malignancies-the PSOGI-ESGO-ISSPP Lyon consensus. · Lancet Oncol, 2026 · PMID 41926971

Metabolic surgery mitigates early kidney injury in obese youth with diabetes by
suppressing mTORC1/JAK/STAT signaling. · J Clin Invest, 2026 · PMID 41665972

Efficacy and safety of LEVI-04 in patients with osteoarthritis of the knee: a
randomised, double-blind, placebo-controlled, phase 2 trial. · Lancet, 2026 · PMID 41905364

Delivery of potential natural disease-modifying osteoarthritis drugs: Beyond
polyphenols and flavonoids. · Biomed Pharmacother, 2026 · PMID 41904894

Standardised formal resuscitation training programmes for reducing mortality and
morbidity in newborn infants. · Cochrane Database Syst Rev, 2026 · PMID 41925066

Sequenced Care Pathway vs Pain Navigator Pathway for Veterans With Low Back
Pain: The AIM-Back Cluster Randomized Clinical Trial. · JAMA Netw Open, 2026 · PMID 41926124

Peer support intervention (ABA-feed) to improve breastfeeding: UK based,
multicentre, parallel group, randomised controlled trial. · BMJ, 2026 · PMID 41916664

Midline catheter versus peripheral intravenous catheter for intravenous
treatment in hospitalized children. · Cochrane Database Syst Rev, 2026 · PMID 41909998

Breast implant insertion funnels for preventing capsular contracture. · Cochrane Database Syst Rev, 2026 · PMID 41909996