18 results match your criteria: "Nashville (M.L.J.); the University of Colorado[Affiliation]"
Background: Immune checkpoint inhibitor (ICI) Kaplan-Meier (KM) curves often show delayed survival benefit followed by long-term survival in a subgroup of patients. Such outcomes can violate the proportional hazards assumption, leading to a loss of statistical power.
Objective: We aimed to determine common trends in delayed separation to inform future ICI clinical trials.
CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors.
Nature
November 2024
Department of Thoracic and Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Article Synopsis
- Dual immune checkpoint blockade (ICB) using CTLA4 and PD-(L)1 inhibitors shows improved anti-tumor effectiveness and immune toxicity compared to PD-(L)1 inhibitors alone in advanced non-small-cell lung cancer (NSCLC) patients.
- Patients with mutations in STK11 and/or KEAP1 genes benefit more from the combination treatment compared to those receiving only PD-(L)1 inhibitors, as shown in the POSEIDON trial.
- The loss of KEAP1 serves as a strong predictor for the success of dual ICB, as it leads to a more favorable outcome by changing the tumor's immune environment to better engage CD4 and CD8 T cells for anti-tumor activity. *
Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial.
Nat Med
March 2024
Department of Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need.
View Article and Find Full Text PDFTarlatamab for Patients with Previously Treated Small-Cell Lung Cancer.
N Engl J Med
November 2023
From Samsung Medical Center, Sungkyunkwan University School of Medicine (M.-J.A.), and Yonsei Cancer Center, Yonsei University College of Medicine (B.C.C.), Seoul, and Seoul National University Bundang Hospital, Seongnam (J.-S.L.) - all in South Korea; Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (E.F.) and Hospital de la Santa Creu i Sant Pau (M. Majem), Barcelona, Hospital Universitari i Politecnic La Fe, Valencia (O.J.-V.), and Hospital Universitario 12 de Octubre, CNIO-H12o Lung Cancer Unit, Complutense University and Ciberonc, Madrid (L.P.-A.) - all in Spain; the Department of Medical Oncology, Saint Loukas Hospital, Thessaloniki, Greece (I.K.); the Department of Respiratory Medicine, Okayama University Hospital, Okayama (K.O.), the Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa (H.I.), and Wakayama Medical University Hospital, Wakayama (H.A.) - all in Japan; Klinische Abteilung für Pneumologie, Universitätsklinikum Krems, Krems, Austria (S. Handzhiev); the Department of Oncology and Radiotherapy and Early Phase Clinical Trials Center, Medical University of Gdansk, Gdansk, Poland (R.D.); the Department of Internal Medicine, Center for Integrated Oncology, University Hospital Cologne, Cologne (J.W.), Lungen Clinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf (M.R.), and the Translational Oncology-Early Clinical Trial Unit, Comprehensive Cancer Center Mainfranken and Bavarian Cancer Research Center, Universitätsklinikum Würzburg, Würzburg (H.-D.H.) - all in Germany; Christie NHS Foundation Trust and University of Manchester, Manchester, United Kingdom (F.B.); West Virginia University Health Sciences Center, Morgantown (J.B.A.); the Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, the Netherlands (A.-M.C.D.); Dana-Farber Cancer Institute, Harvard Medical School, Boston (J.S.); the Division of Hematology-Oncology, Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (T.K.O.), and Fox Chase Cancer Center, Philadelphia (H.B.) - both in Pennsylvania; Winship Cancer Institute of Emory University, Atlanta (S.S.R.); Sarah Cannon Research Institute at Tennessee Oncology, Nashville (M.L.J.); and Amgen, Thousand Oaks, CA (S. Huang, S.M., M. Minocha, T.J., P.M., E.S.A.).
Article Synopsis
- Tarlatamab is a bispecific T-cell engager immunotherapy that showed promising results in a phase 1 trial for patients with previously treated small-cell lung cancer.
- In a phase 2 trial involving 220 patients, tarlatamab was administered intravenously every 2 weeks at doses of 10 mg or 100 mg, with an objective response rate of 40% and 32% respectively.
- The study found that common side effects included cytokine-release syndrome, decreased appetite, and fever, with overall survival rates at 9 months being 68% for the 10-mg group and 66% for the 100-mg group.
Early Changes in Circulating Cell-Free KRAS G12C Predict Response to Adagrasib in KRAS Mutant Non-Small Cell Lung Cancer Patients.
Clin Cancer Res
August 2023
Belfer Center of Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
Purpose: Non-invasive monitoring of circulating tumor DNA (ctDNA) has the potential to be a readily available measure for early prediction of clinical response. Here, we report on early ctDNA changes of KRAS G12C in a Phase 2 trial of adagrasib in patients with advanced, KRAS G12C-mutant lung cancer.
Experimental Design: We performed serial droplet digital PCR (ddPCR) and plasma NGS on 60 KRAS G12C-mutant patients with lung cancer that participated in cohort A of the KRYSTAL-1 clinical trial.
Autologous T cell therapy for MAGE-A4 solid cancers in HLA-A*02 patients: a phase 1 trial.
Nat Med
January 2023
Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ).
View Article and Find Full Text PDFMethylprednisolone for Heart Surgery in Infants - A Randomized, Controlled Trial.
N Engl J Med
December 2022
From the Duke Pediatric and Congenital Heart Center (K.D.H., J.W.T., J.S.L.) and the Duke Clinical Research Institute (K.D.H., S.M.O., J.L.K., D.S.G., J.S.L.) - both in Durham, NC; Vanderbilt University Medical Center, Nashville (P.J.K., H.S.B., D.P.B.); the University of Florida Congenital Heart Center, Gainesville (J.P.J., M.B.); Johns Hopkins University School of Medicine, Baltimore (M.L.J., B.M.); the Medical University of South Carolina, Charleston (E.M.G.); the UPMC Children's Hospital of Pittsburgh, Pittsburgh (B.B.); the Section of Pediatric Cardiac Anesthesiology, Texas Children's Hospital, Department of Anesthesiology, Baylor College of Medicine, Houston (A.R., D.F.V.), and the Division of Cardiology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas (R.B.); the University of Utah-Primary Children's Hospital, Salt Lake City (A.S.H.); the University of Southern California and the Heart Institute, Children's Hospital of Los Angeles - both in Los Angeles (S.R.K.); the University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati (A.B.), the Division of Pediatric Cardiac Surgery, Heart Vascular and Thoracic Institute, Cleveland Clinic Children's, Cleveland (T.K.), and the Department of Cardiothoracic Surgery, Nationwide Children's Hospital, and Ohio State University, Columbus (P.I.M.) - all in Ohio; the Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago (E.W.), and the Advocate Children's Heart Institute, Advocate Children's Hospital, Division of Pediatric Cardiac Critical Care, Oak Lawn (A.H.V.B.) - both in Illinois; the Division of Cardiovascular Surgery, Children's Minnesota, Minneapolis (D.O.); the Section of Pediatric Cardiothoracic Surgery, Washington University School of Medicine, St. Louis (P.E.); the Division of Cardiology, Department of Pediatrics, Heart Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora (J.S.K.); Children's Wisconsin, Medical College of Wisconsin, Milwaukee (J.P.S.); and the Division of Pediatric Cardiology, New York-Presbyterian Hospital-Columbia University Irving Medical Center, New York (B.R.A.), and the University of Rochester Medical Center, Rochester (M.F.S.) - both in New York.
Background: Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass is unknown.
Methods: We conducted a multicenter, prospective, randomized, placebo-controlled, registry-based trial involving infants (<1 year of age) undergoing heart surgery with cardiopulmonary bypass at 24 sites participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database. Registry data were used in the evaluation of outcomes.
Adagrasib in Non-Small-Cell Lung Cancer Harboring a Mutation.
N Engl J Med
July 2022
From the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute (P.A.J.), and Massachusetts General Hospital (R.S.H.) - both in Boston; the Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College (G.J.R.), and Perlmutter Cancer Center, New York University Langone Health (J.K.S.), New York, and the Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo (E.Y.) - all in New York; the Henry Ford Cancer Institute, Detroit (S.M.G.); the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), the University of California San Diego Moores Cancer Center, La Jolla (L.B.), and Mirati Therapeutics, San Diego (K.A., H.D.-T., T.K., K.V., X.Y., J.G.C., R.C.C.) - all in California; the Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora (J.M.P.); Sarah Cannon Research Institute at Tennessee Oncology, Nashville (M.L.J.); the Department of Oncology, Mayo Clinic, Rochester, MN (K.L.); the University of Texas M.D. Anderson Cancer Center, Houston (M.V.N.) and US Oncology Research, The Woodlands (A.I.S.) - both in Texas; Cleveland Clinic Taussig Cancer Institute, Cleveland (N.A.P.); the Division of Medical Oncology, Department of Internal Medicine, and the Department of Cancer Biology, University of Kansas Medical Center, Kansas City (J.Z.); and Virginia Cancer Specialists and NEXT Oncology Virginia - both in Fairfax (A.I.S.).
Background: Adagrasib, a KRAS inhibitor, irreversibly and selectively binds KRAS, locking it in its inactive state. Adagrasib showed clinical activity and had an acceptable adverse-event profile in the phase 1-1b part of the KRYSTAL-1 phase 1-2 study.
Methods: In a registrational phase 2 cohort, we evaluated adagrasib (600 mg orally twice daily) in patients with -mutated non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy and anti-programmed death 1 or programmed death ligand 1 therapy.
Association of Premature Menopause With Coronary Artery Calcium: The CARDIA Study.
Circ Cardiovasc Imaging
November 2021
Division of Cardiology, Department of Medicine (P.M.F., D.M.L.-J., S.S.K.), Northwestern University Feinberg School of Medicine, Chicago, IL.
Acquired Resistance to KRAS Inhibition in Cancer.
N Engl J Med
June 2021
From Dana-Farber Cancer Institute (M.M.A., S.L., J.D., J.O.J., K.E.L., H.F., K.M.H., B.M.W., P.A.J., A.J.A.), Massachusetts General Hospital (R.S.H., Y.P.H.), and Brigham and Women's Hospital (L.M.S., A.J.A.), Boston, and Broad Institute of MIT and Harvard (S.L., X.Y., N.S.P., D.E.R., K.M.H., A.J.A.) and Foundation Medicine (J.L., A.B.S.), Cambridge - all in Massachusetts; Henry Ford Cancer Institute, Detroit (I.I.R.); Memorial Sloan Kettering Cancer Center, New York (K.C.A., G.J.R., P.L.); Chao Family Comprehensive Cancer Center, University of California, Irvine, School of Medicine, Orange (V.W.Z., S.S.Z., S.-H.I.O.), Boundless Bio, La Jolla (J.W., J.C.), and Mirati Therapeutics, San Diego (L.D.E., L.W., J.D.L., P.O., J.G.C.) - all in California; Sarah Cannon Research Institute, Tennessee Oncology/OneOncology, Nashville (M.L.J.); the University of Colorado, Aurora (T.P.); and Resolution Bioscience, Kirkland, WA (L.P.L., K.G., M.L.).
Article Synopsis
- New drugs called KRAS inhibitors, like adagrasib and sotorasib, help treat some cancers but sometimes stop working because the cancer cells become resistant.
- In a study with 38 patients, researchers found that almost half had changes in their cancer cells that allowed them to resist the treatment, with some having more than one change.
- The study shows that we need better strategies to deal with this resistance to continue helping cancer patients effectively.
Risk-Based Approach for the Prediction and Prevention of Heart Failure.
Circ Heart Fail
February 2021
Division of Cardiology, Department of Medicine, Feinberg School of Medicine (A.S., C.W.Y., S.J.S., E.M.N., D.M.L.-J., S.S.K.), Northwestern University, Chicago, IL.
Targeted prevention of heart failure (HF) remains a critical need given the high prevalence of HF morbidity and mortality. Similar to risk-based prevention of atherosclerotic cardiovascular disease, optimal HF prevention strategies should include quantification of risk in the individual patient. In this review, we discuss incorporation of a quantitative risk-based approach into the existing HF staging landscape and the clinical opportunity that exists to translate available data on risk estimation to help guide personalized decision making.
View Article and Find Full Text PDFOvercoming MET-Dependent Resistance to Selective RET Inhibition in Patients with RET Fusion-Positive Lung Cancer by Combining Selpercatinib with Crizotinib.
Clin Cancer Res
January 2021
Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Purpose: The proto-oncogene encodes a receptor tyrosine kinase that is activated by gene fusion in 1%-2% of non-small cell lung cancers (NSCLC) and rarely in other cancer types. Selpercatinib is a highly selective RET kinase inhibitor that has recently been approved by the FDA in lung and thyroid cancers with activating gene fusions and mutations. Molecular mechanisms of acquired resistance to selpercatinib are poorly understood.
View Article and Find Full Text PDFReply to Tran et al.: Dimeric KRAS protein-protein interaction stabilizers.
Proc Natl Acad Sci U S A
February 2020
Discovery Research, Boehringer Ingelheim RCV GmbH & Co KG, 1120 Vienna, Austria;
Drugging an undruggable pocket on KRAS.
Proc Natl Acad Sci U S A
August 2019
Discovery Research, Boehringer Ingelheim Regional Center Vienna GmbH & Co KG, 1120 Vienna, Austria;
The 3 human RAS genes, KRAS, NRAS, and HRAS, encode 4 different RAS proteins which belong to the protein family of small GTPases that function as binary molecular switches involved in cell signaling. Activating mutations in RAS are among the most common oncogenic drivers in human cancers, with KRAS being the most frequently mutated oncogene. Although KRAS is an excellent drug discovery target for many cancers, and despite decades of research, no therapeutic agent directly targeting RAS has been clinically approved.
View Article and Find Full Text PDFCoronary Artery Calcium From Early Adulthood to Middle Age and Left Ventricular Structure and Function.
Circ Cardiovasc Imaging
June 2019
Division of Cardiology, Johns Hopkins University, Baltimore, MD (G.S.Y., H.T.M., B.A.-V., H.D.V., C.C.N., M.R.O., J.A.C.L.).
Background The relationship of coronary artery calcium (CAC) with adverse cardiac remodeling is not well established. We aimed to study the association of CAC in middle age and change in CAC from early adulthood to middle age with left ventricular (LV) function. Methods CAC score was measured by computed tomography at CARDIA study (Coronary Artery Risk Development in Young Adults) year-15 examination and at year-25 examination (Y25) in 3043 and 3189 participants, respectively.
View Article and Find Full Text PDFFirst-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer.
N Engl J Med
December 2018
From Vanderbilt University Medical Center (L. Horn) and Sarah Cannon Research Institute-Tennessee Oncology (M.L.J.), Nashville; Mayo Clinic, Rochester, MN (A.S.M.); Mazowieckie Centrum Leczenia Chorób Płuc i Gruźlicy, Otwock (A. Szczęsna), and Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie w Warszawie, Warsaw (M.K.) - both in Poland; Thomayerova Nemocnice, Pneumologická Klinika 1.LF UK, Prague, Czech Republic (L. Havel); the Department of Respiratory and Critical Care Medicine (M.J.H.) and the 2nd Department of Respiratory and Critical Care Medicine (F.H.), Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology-Sozialmedizinisches Zentrum Baumgartner Höhe, Otto-Wagner-Spital, Vienna; Semmelweis Egyetem ÁOK, Pulmonológiai Klinika, Budapest, Hungary (G.L.); the Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo (M.N.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); State Key Laboratory of South China, Chinese University of Hong Kong, Hong Kong (T.M.), and F. Hoffmann-La Roche, Shanghai (J.L.) - both in China; Genentech, South San Francisco, CA (S.L., D.S.S., B.D., A.L.-C., F.K., W.L., A. Sandler); and Georgetown University, Washington DC (S.V.L.).
Background: Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)-programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy.
Methods: We conducted this double-blind, placebo-controlled, phase 3 trial to evaluate atezolizumab plus carboplatin and etoposide in patients with extensive-stage small-cell lung cancer who had not previously received treatment.
PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma.
N Engl J Med
July 2018
From the Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston (M.R.M.), and South Texas Accelerated Research Therapeutics (START), San Antonio (K.P.P.) - both in Texas; the Department of Medical Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC (D.R., A.A.T.), the Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, VIC (A.G.), the Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, WA (A.M.L.), and Royal Brisbane and Women's Hospital and University of Queensland, Brisbane (B.G.M.H.) - all in Australia; the Department of Dermatology, Brigham and Women's Hospital (C.D.S.), the Department of Dermatology, Harvard Medical School (C.D.S.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (G.R.) - all in Boston; Schleswig-Holstein University Hospital, Kiel (A.H.), and University Hospital Essen, Essen and German Cancer Consortium, Essen (D.S.) - both in Germany; University of Colorado Denver, School of Medicine, Aurora (K.D.L.); the Departments of Head and Neck-Endocrine Oncology (C.H.C.) and Cutaneous Oncology (N.I.K.), H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; the Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis (L.H.-A.); the Department of Dermatology, Stanford University School of Medicine, Redwood City (A.L.S.C.), and the Division of Dermatology, City of Hope, Duarte (B.M.) - both in California; the Department of Medicine, Head and Neck Medical Oncology, Memorial Sloan Kettering Cancer Center, New York (L.A.D.), and Regeneron Pharmaceuticals, Tarrytown (F.S., M.M., K.M., G.D.Y., I.L., M.G.F.) - both in New York; Regeneron Pharmaceuticals, Basking Ridge, NJ (B.G., S.L., J.L., J.B., E.S.); University of Arizona Cancer Center, Tucson (H.M.B.), and Banner MD Anderson Cancer (J.H.) and the Department of Medical Oncology, Banner MD Anderson Cancer Center (J.N.), Gilbert - all in Arizona; Medical Oncology Department, Vall D'Hebron University Hospital (I.B.), and Institut Català D'Oncologia, Oncobell Program (IDIBELL), L'Hospitalet de Llobregat (M.G.-M.), Barcelona, and START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid (V.M.) - all in Spain; Sarah Cannon Research Institute, Nashville (M.L.J.); and the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta (T.K.O.).
Background: No systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma.
View Article and Find Full Text PDFRelating structural and functional brainstem connectivity to disease measures in epilepsy.
Neurology
July 2018
From the Departments of Neurological Surgery (D.J.E., P.E.K.), Biomedical Engineering (D.J.E., H.F.J.G., P.E.K., B.A.L., V.L.M.), Radiology and Radiological Sciences (D.J.E., B.B.R., J.C.G., B.A.L., V.L.M.), Psychiatry and Behavioral Sciences (M.L.J.), and the Vanderbilt University Institute of Imaging Science (D.J.E., H.F.J.G., B.B.R., J.C.G., B.A.L., V.L.M.), Vanderbilt University Medical Center, Nashville, TN.
Objective: While epilepsy studies rarely examine brainstem, we sought to examine the hypothesis that temporal lobe epilepsy (TLE) leads to subcortical arousal center dysfunction, contributing to neocortical connectivity and neurocognitive disturbances.
Methods: In this case-control study of 26 adult patients with TLE and 26 controls, we used MRI to measure structural and functional connectivity of the cuneiform/subcuneiform nuclei (CSC), pedunculopontine nucleus, and ventral tegmental area. Ascending reticular activating system connectivity patterns were related to neuropsychological and disease measures.