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Mashup Score: 24Non–Small Cell Lung Cancer Metastatic Without Oncogenic Alterations - 14 hour(s) ago
This overview provides a thorough review of current treatment approaches for first-line management of nononcogenic addicted non–small cell lung cancer. We also address pertinent clinical decision-making queries encountered in everyday practice, such as the optimal treatment strategy for PD-L1–high patients, predictive factors for response to immune checkpoint inhibitors (ICI) both in terms of patient and cancer characteristics, the potential benefits of dual checkpoint blockade, and the unresolved issue of safe discontinuation strategies for long-term responders. Around one in five patients falls into this latter category while the majority develop either primary or acquired resistance to ICI-based first-line therapy, necessitating effective subsequent lines of treatment. Docetaxel, with or without combination of antiangiogenic agents, serves as the backbone of treatment, although evidence in the post-ICI setting is limited. Given that an inflamed tumor microenvironment (TME) is crucia
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Mashup Score: 34NECTIN4 Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer - 16 hour(s) ago
PURPOSE The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. NECTIN4 is located on chromosome 1q23.3, and 1q23.3 gains represent frequent copy number variations (CNVs) in urothelial cancer. Here, we aimed to evaluate NECTIN4 amplifications as a genomic biomarker to predict EV response in patients with mUC. MATERIALS AND METHODS We established a NECTIN4-specific fluorescence in situ hybridization (FISH) assay to assess the predictive value of NECTIN4 CNVs in a multicenter EV-treated mUC patient cohort (mUC-EV, n = 108). CNVs were correlated with membranous NECTIN4 protein expression, EV treatment responses, and outcomes. We also assessed the prognostic value of NECTIN4 CNVs measured in metastatic biopsies of non–EV-treated mUC (mUC-non-EV, n = 103). Furthermore, we queried The Cancer Genome Atlas (TCGA) data sets (10,712
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Mashup Score: 3Design and Implementation of an Opt-Out, End-to-End, Preemptive DPYD Testing Program for Patients Planned for a Systemic Fluoropyrimidine - 20 hour(s) ago
PURPOSE Several allelic variants of the gene DPYD encoding dihydropyrimidine dehydrogenase (DPD) are associated with impaired metabolism of the systemic fluoropyrimidine fluorouracil (5FU) and its oral prodrug, capecitabine, which elevates the risk for severe toxicity. Following a patient death related to capecitabine toxicity in which DPD deficiency was suspected, a multidisciplinary advisory panel was convened to develop an institution-wide approach to future patients planned for a systemic fluoropyrimidine. METHODS The panel selected an opt-out testing strategy which focused on developing reliable processes to collect and report test results and targeted education. An electronic health record–based automated reminder was designed to activate when a 5FU- or capecitabine-containing chemotherapy regimen was ordered for a patient without prior exposure to either agent and without a prior DPYD sequencing test result. DPYD testing was standardized across all sites of care, and a closed lo
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A multiprong set of interventions led to ⬆️ rate (baseline 26% to a sustained rate of >90%) of preemptive #DPYD testing for pts planned for a systemic fluoropyrimidine. Implementing an opt-out, reminder-based program may save lives. ➡️ https://t.co/Gty41hJl2o #impsci @Labrat3 https://t.co/td4BzenH9s
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Mashup Score: 34NECTIN4 Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer - 1 day(s) ago
PURPOSE The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. NECTIN4 is located on chromosome 1q23.3, and 1q23.3 gains represent frequent copy number variations (CNVs) in urothelial cancer. Here, we aimed to evaluate NECTIN4 amplifications as a genomic biomarker to predict EV response in patients with mUC. MATERIALS AND METHODS We established a NECTIN4-specific fluorescence in situ hybridization (FISH) assay to assess the predictive value of NECTIN4 CNVs in a multicenter EV-treated mUC patient cohort (mUC-EV, n = 108). CNVs were correlated with membranous NECTIN4 protein expression, EV treatment responses, and outcomes. We also assessed the prognostic value of NECTIN4 CNVs measured in metastatic biopsies of non–EV-treated mUC (mUC-non-EV, n = 103). Furthermore, we queried The Cancer Genome Atlas (TCGA) data sets (10,712
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Mashup Score: 34NECTIN4 Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer - 2 day(s) ago
PURPOSE The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. NECTIN4 is located on chromosome 1q23.3, and 1q23.3 gains represent frequent copy number variations (CNVs) in urothelial cancer. Here, we aimed to evaluate NECTIN4 amplifications as a genomic biomarker to predict EV response in patients with mUC. MATERIALS AND METHODS We established a NECTIN4-specific fluorescence in situ hybridization (FISH) assay to assess the predictive value of NECTIN4 CNVs in a multicenter EV-treated mUC patient cohort (mUC-EV, n = 108). CNVs were correlated with membranous NECTIN4 protein expression, EV treatment responses, and outcomes. We also assessed the prognostic value of NECTIN4 CNVs measured in metastatic biopsies of non–EV-treated mUC (mUC-non-EV, n = 103). Furthermore, we queried The Cancer Genome Atlas (TCGA) data sets (10,712
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Mashup Score: 6Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update Clinical Insights - 2 day(s) ago
Published online: April 25, 2024 Request permissions for this article. Yale University School of Medicine and VA Connecticut Healthcare System, West Haven, CT American Society of Clinical Oncology, Alexandria, VA Memorial Sloan Kettering Cancer Center, New York, NY Weill Medical College at Cornell University, New York, NY Tri nity College Dublin Medical School, Dublin, Ireland Geffen School of Medicine, UCLA, Los Angeles, CA Penn Medicine, Philadelphia, PA University of California, San Francisco, San
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Mashup Score: 8
6577 Background: Wearable physical activity monitors (PAMs) provide a degree of functional assessment not possible with prior clinical instruments. Subjective assessments of functional status are prone to inaccuracy and current objective assessment techniques are limited to the research setting. The relevance of physical activity monitors (PAMs) to measure functional status in cancer patients is unclear. The feasibility of using these devices in cancer patients is not known. Methods: This is a prospective pilot trial of a commercially available PAM in cancer patients. Patients with Eastern Cooperative Group performance status (ECOG PS) 0-2 receiving systemic therapy at an NCI Designated Comprehensive Cancer Center were enrolled. (NCT02583815). The primary objective was to determine feasibility of PAM use, defined as device use of more than 50% of the study observation period. Secondary objectives were to correlate PAM-reported measures: median, minimum and maximum steps/day, minutes of
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Mashup Score: 14Landscape of KRASG12C, Associated Genomic Alterations, and Interrelation With Immuno-Oncology Biomarkers in KRAS-Mutated Cancers - 3 day(s) ago
PURPOSE Promising single-agent activity from sotorasib and adagrasib in KRASG12C-mutant tumors has provided clinical evidence of effective KRAS signaling inhibition. However, comprehensive analysis of KRAS-variant prevalence, genomic alterations, and the relationship between KRAS and immuno-oncology biomarkers is lacking. MATERIALS AND METHODS Retrospective analysis of deidentified records from 79,004 patients with various cancers who underwent next-generation sequencing was performed. Fisher’s exact test evaluated the association between cancer subtypes and KRAS variants. Logistic regression assessed KRASG12C comutations with other oncogenes and the association between KRAS variants and immuno-oncology biomarkers. RESULTS Of the 79,004 samples assessed, 13,758 (17.4%) harbored KRAS mutations, with 1,632 (11.9%) harboring KRASG12C and 12,126 (88.1%) harboring other KRAS variants (KRASnon-G12C). Compared with KRASnon-G12C across all tumor subtypes, KRASG12C was more prevalent in females
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Mashup Score: 4Somatic Genomic Testing in Patients With Metastatic or Advanced Cancer: ASCO Provisional Clinical Opinion - 3 day(s) ago
PURPOSE An ASCO provisional clinical opinion offers timely clinical direction to ASCO’s membership following publication or presentation of potentially practice-changing data from major studies. This provisional clinical opinion addresses the appropriate use of tumor genomic testing in patients with metastatic or advanced solid tumors. CLINICAL CONTEXT An increasing number of therapies are approved to treat cancers harboring specific genomic biomarkers. However, there is a lack of clarity as to when tumor genomic sequencing should be ordered, what type of assays should be performed, and how to interpret the results for treatment selection. PROVISIONAL CLINICAL OPINION Patients with metastatic or advanced cancer should undergo genomic sequencing in a certified laboratory if the presence of one or more specific genomic alterations has regulatory approval as biomarkers to guide the use of or exclusion from certain treatments for their disease. Multigene panel–based assays should be used i
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Mashup Score: 1Leveraging machine learning technology to efficiently identify and match patients for precision oncology clinical trials. - 3 day(s) ago
e13588 Background: Pre-screening for clinical trials is becoming more challenging as inclusion/exclusion criteria becomes increasingly complex. Oncology precision medicine provides an exciting opportunity to simplify this process and quickly match patients with trials by leveraging machine learning technology. The Tempus TIME Trial site network matches patients to relevant, open, and recruiting clinical trials, personalized to each patient’s clinical and molecular biology. Methods: Tempus screens patients at sites within the TIME Trial Network to find high-fidelity matches to clinical trials. The patient records include documentation submitted alongside NGS orders as well as electronic medical records (EMR) ingested through EMR Integrations. While Tempus-sequenced patients were automatically matched to trials using a Tempus-built matching application, EMR records were run through a natural language processing (NLP) data abstraction model to identify patients with an actionable gene of
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Non–Small Cell Lung Cancer Metastatic Without Oncogenic Alterations | American Society of Clinical Oncology Educational Book https://t.co/5jTCWpVatj #ASCO24 #LCSM @MartinReck2