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Issues in Oncology
Genomics/Genetics

Patients With Cancer and DPYD Variant Alleles: Outcomes With Reduced-Dose Fluoropyrimidine Therapy

In an analysis reported in the Journal of Clinical Oncology, Knikman et al found that reduced doses of fluoropyrimidine therapy in patients with cancer with DPYD variant alleles did not result in poorer outcomes vs DPYD wild-type controls receiving full fluoropyrimidine doses. Study Details The...

genomics/genetics

Aaron C. Tan, PhD, MBBS, on Circulating Tumor DNA: Early Biomarker of Therapeutic Response in Phase I Trials

Aaron C. Tan, PhD, MBBS, of the National Cancer Centre Singapore, discusses new findings on early evaluation of circulating tumor DNA via low-pass whole-genome sequencing. The results of his study suggest this method may represent an early pharmacodynamic biomarker of therapeutic response (particularly for targeted treatments) that may influence decisions on dose determination (Abstract 23).

Pancreatic Cancer
Genomics/Genetics

Germline Predisposition and Homologous Recombination Deficiency in Pancreatic Acinar Cell Carcinoma

In a study reported in the Journal of Clinical Oncology, Mandelker et al found that pancreatic acinar cell carcinoma was associated with a high prevalence of BRCA2 germline pathogenic variants and genomic features of homologous recombination deficiency (HRD). The study involved somatic and germline ...

Myelodysplastic Syndromes
Genomics/Genetics

Allogeneic HCT Outcomes in Patients With MDS and High-Risk Genetics

In a genetic analysis from the Blood and Marrow Transplant Clinical Trials Network 1102 Study reported in the Journal of Clinical Oncology, Versluis et al found that allogeneic hematopoietic cell transplantation (HCT) improved overall survival compared with non-HCT treatment in patients with...

Genomics/Genetics

23andMe Granted FDA 510(k) Clearance to Report Additional BRCA Variants

23andMe has announced that the company has received a U.S. Food and Drug Administration (FDA) 510(k) clearance to expand its existing BRCA1/BRCA2 (Selected Variants) Genetic Health Risk Report. The clearance allows 23andMe to report an additional 41 variants in the BRCA1 and BRCA2 genes known to be ...

Solid Tumors
Genomics/Genetics

Divarasib in Patients With Advanced Solid Tumors and a KRAS G12C Mutation

In a phase I study reported in The New England Journal of Medicine, Sacher et al found that the covalent KRAS G12C inhibitor divarasib (also referred to as GDC-6036) produced durable responses in patients with advanced or metastatic solid tumors with a KRAS G12C mutation. In the study, 137 patients ...

Leukemia
Genomics/Genetics

Understanding How TET2 Gene Deficiency May Fuel Development of AML

Researchers may have identified how low levels of the TET2 gene may fuel rapid cancer growth in patients with acute myeloid leukemia (AML), according to a recent study published by Li et al in Cell Stem Cell. Background AML is distinguished by the rapid division and metastasis of immature leukemia...

Breast Cancer
Genomics/Genetics

Researchers May Have Identified Several New Breast Cancer Susceptibility Genes

Researchers have identified genes that may be associated with breast cancer and could eventually be included in tests to identify high-risk patients, according to a recent study published by Wilcox et al in Nature Genetics. Background Currently, genetic tests for breast cancer consider a few genes...

Breast Cancer
Gynecologic Cancers
Genomics/Genetics

Therapeutic Implications of DNA Repair Discoveries in Patients With Homologous Recombination Deficiencies

Long-molecule scars may help identify patients with BRCA1- and BRCA2-deficient cancer types, according to a recent study published by Setton et al in Nature. Background Once DNA is damaged by toxins, radiation, or normal cell division, human cells must continually fix DNA breaks to survive. When...

Bladder Cancer
Genomics/Genetics

Diagnosing Early-Stage Bladder Cancer in Patients With Hematuria: Novel mePENK Test

Researchers have found that the new PENK methylation (mePENK) test could potentially pave the way for a breakthrough in early bladder cancer detection in patients with hematuria, according to a novel study published by Oh et al in The Journal of Molecular Diagnostics. The findings could reduce the...

Bladder Cancer
Genomics/Genetics

Expert Point of View: Daniel P. Petrylak, MD

“Clinically, the implications [of the THOR trial] are clear in that all metastatic urothelial cancers should be tested for FGFR mutations,” stated invited discussant Daniel P. Petrylak, MD, of Yale School of Medicine. “This should be done at the beginning of treatment for metastatic disease, as it...

Bladder Cancer
Genomics/Genetics

THOR Trial: Erdafitinib Improves Outcomes vs Chemotherapy in FGFR-Altered Advanced Urothelial Carcinoma

Targeted treatment with the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib significantly improved overall survival, progression-free survival, and objective response rates compared with investigator’s choice of chemotherapy in patients with advanced urothelial cancers and FGFR2/3...

Prostate Cancer
Genomics/Genetics

Rucaparib vs Physician’s Choice of Single-Agent Therapy in BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer

As reported in The New England Journal of Medicine by Karim Fizazi, MD, PhD, of Gustave Roussy Institute, Paris-Saclay University, and colleagues, the phase III TRITON3 trial has shown significantly improved progression-free survival with rucaparib vs physician-selected single-agent therapy in the...

Prostate Cancer
Genomics/Genetics

FDA Approves Niraparib and Abiraterone Acetate Plus Prednisone for BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer

On August 11, the U.S. Food and Drug Administration (FDA) approved the fixed-dose combination of niraparib and abiraterone acetate (Akeega), with prednisone, for adult patients with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer, as determined by...

Lung Cancer
Genomics/Genetics

FDA Approves Pralsetinib for RET Fusion–Positive NSCLC

On August 9, the U.S. Food and Drug Administration (FDA) granted regular approval to pralsetinib (Gavreto) for adults with metastatic RET fusion–positive non–small cell lung cancer (NSCLC), as detected by an FDA-approved test. ARROW Trial Pralsetinib was previously granted accelerated approval for...

Solid Tumors
Genomics/Genetics

Erdafitinib for Patients With FGFR-Altered Advanced Solid Tumors

In the phase II RAGNAR study reported in The Lancet Oncology, Shubham Pant, MBBS, and colleagues found that the pan-FGFR tyrosine kinase inhibitor erdafitinib showed activity in patients with advanced solid tumors with FGFR alterations. Study Details In the ongoing study, 217 patients aged ≥ 12...

Leukemia
Genomics/Genetics

Outcomes in Pediatric ALL With Prolonged Therapy for IKZF1 Deletion and Reduced Therapy for Other Risk Groups

In a recent study (Dutch Childhood Oncology Group [DCOG] ALL11) reported in the Journal of Clinical Oncology, Pieters et al found that modifications in therapy appeared to improve outcomes and reduce drug exposure in pediatric patients with acute lymphoblastic leukemia (ALL) compared with treatment ...

Skin Cancer
Genomics/Genetics

Atezolizumab, Vemurafenib, and Cobimetinib in Patients With BRAF V600–Mutated Melanoma and CNS Metastases

A revised report of findings from the phase II TRICOTEL study of atezolizumab, vemurafenib, and cobimetinib in patients with melanoma and central nervous system (CNS) metastases was published in The Lancet Oncology by Reinhard Dummer, MD, and colleagues. The first version of trial findings,...

Bladder Cancer
Genomics/Genetics

Expert Point of View: Daniel P. Petrylak, MD

“Clinically, the implications [of the THOR trial] are clear in that all metastatic urothelial cancers should be tested for FGFR mutations,” stated invited discussant Daniel P. Petrylak, MD, of Yale School of Medicine. “This should be done at the beginning of treatment for metastatic disease, as it...

Bladder Cancer
Genomics/Genetics

THOR Trial: Erdafitinib Improves Outcomes vs Chemotherapy in FGFR-Altered Advanced Urothelial Carcinoma

Targeted treatment with the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib significantly improved overall survival, progression-free survival, and objective response rates compared with investigator’s choice of chemotherapy in patients with advanced urothelial cancers and FGFR2/3...

Leukemia
Genomics/Genetics

FDA Approves Quizartinib for Newly Diagnosed FLT3-ITD–Positive Acute Myeloid Leukemia

On July 20, the U.S. Food and Drug Administration (FDA) approved quizartinib (Vanflyta) with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adults with newly diagnosed acute...

Lung Cancer
Genomics/Genetics

Adjuvant Osimertinib in Resected EGFR-Mutant NSCLC: Overall Survival Analysis of the ADAURA Trial

As reported in The New England Journal of Medicine by Masahiro Tsuboi, MD, and colleagues, the planned final overall survival analysis of the phase III ADAURA trial has shown a significant benefit with osimertinib vs placebo in patients with resected EGFR-mutant non–small cell lung cancer (NSCLC)....

Lung Cancer
Genomics/Genetics

Lazertinib vs Gefitinib in the First-Line Treatment of EGFR-Mutated Advanced NSCLC

In a phase III trial (LASER301) reported in the Journal of Clinical Oncology, Byoung Chul Cho, MD, PhD, and colleagues found that lazertinib improved progression-free survival vs gefitinib in the first-line treatment of EGFR-mutated advanced non–small cell lung cancer (NSCLC). As stated by the...

Lung Cancer
Genomics/Genetics

APOBEC3A Protein May Be Linked to Drug Resistance in Patients With NSCLC

Researchers have uncovered how non–small cell lung cancer (NSCLC) tumors may develop drug resistance over time and identified the APOBEC3A protein as a potential target for novel cancer therapeutics, according to a study published by Isozaki et al in Nature. The findings point to potential...

Lung Cancer
Genomics/Genetics

Use of Zipalertinib in Previously Treated Patients With Advanced NSCLC and EGFR Exon 20 Insertions

In a phase I/IIa study reported in the Journal of Clinical Oncology, Piotrowska et al found that the EGFR tyrosine kinase inhibitor zipalertinib showed activity and an acceptable safety profile in previously treated patients with advanced non–small cell lung cancer (NSCLC) and EGFR exon 20...

Lung Cancer
Genomics/Genetics

Pembrolizumab-Based Combination Therapies May Improve Outcomes in Advanced NSCLC

Researchers have revealed that combining pembrolizumab with other treatments may reduce the size of target tumors, resulting in a higher response rate for patients with advanced non–small cell lung cancer (NSCLC), according to a recent study published by Gutierrez et al in Nature Medicine. “We are...

Colorectal Cancer
Genomics/Genetics

Germline Variants in Colorectal Cancer Susceptibility Genes by Race/Ethnicity in Patients With Early-Onset Colorectal Cancer

In a study reported in the Journal of Clinical Oncology, Seagle et al identified the prevalence of germline colorectal cancer susceptibility gene variants according to race and ethnicity among patients with early-onset colorectal cancer. Study Details The study involved patients aged 15 to 49 years ...

Hepatobiliary Cancer
Genomics/Genetics

EGFR and ERBB2 Mutations May Be Associated With Lenvatinib-Resistant Hepatocellular Carcinoma

A genetic marker involving the EGFR and ERBB2 genes may be predictive of which patients with hepatocellular carcinoma are most likely to develop resistance to lenvatinib, according to a study published by Lim et al in Gastroenterology. The new findings could help researchers develop alternative...

Colorectal Cancer
Genomics/Genetics

Expert Point of View: Lisa Newman, MD, MPH, FACS, FASCO

Commenting on this study on clinical genomic profiling for colorectal cancer, Lisa Newman, MD, MPH, FACS, FASCO, Chief of the Section of Breast Surgery and leader of the Multidisciplinary Breast Oncology Programs at Weill Cornell Medicine and NewYork-Presbyterian, commended the authors for...

Colorectal Cancer
Genomics/Genetics

Retrospective Study Finds Black Patients With Colorectal Cancer Had Fewer Actionable Genomic Mutations Than White Patients

Black individuals have a higher incidence of colorectal cancer than White individuals, and their outcomes are worse. Undoubtedly, reasons for this are multifaceted, but the disparity in outcomes may be partly explained by genomic differences, documented in a large retrospective study presented at...

Colorectal Cancer
Genomics/Genetics

Effect of Upregulated KDM5D Gene on Y Chromosome in Male Patients With KRAS-Mutated Colorectal Cancer

Researchers have revealed that the KDM5D gene on the Y chromosome, which is upregulated in KRAS-mutated colorectal cancer, may be responsible for increasing tumor cell invasiveness and reducing antitumor immunity in male patients, according to a recent study published by Li et al in Nature. The new ...

Bladder Cancer
Genomics/Genetics

Loss of Y Chromosome in Men and Bladder Cancer Progression

Researchers have found that the loss of the Y chromosome, a common impact of the aging process in men, may help cancer cells evade the body’s immune system and result in aggressive bladder cancer—but it may also render the disease more vulnerable and responsive to immune checkpoint...

Prostate Cancer
Genomics/Genetics

FDA Approves Talazoparib With Enzalutamide for HRR Gene–Mutated Metastatic Castration-Resistant Prostate Cancer

On June 20, the U.S. Food and Drug Administration (FDA) approved talazoparib (Talzenna) with enzalutamide for homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer. TALAPRO-2 Efficacy was evaluated in TALAPRO-2 (ClinicalTrials.gov identifier...

Lung Cancer
Genomics/Genetics

Encorafenib and Binimetinib in BRAF V600E–Mutant Metastatic NSCLC

In the phase II PHAROS trial reported in the Journal of Clinical Oncology, Gregory J. Riely, MD, PhD, and colleagues found that the combination of encorafenib and binimetinib showed activity in both treatment-naive and previously treated patients with BRAF V600E–mutant metastatic non–small cell...

Breast Cancer
Genomics/Genetics

Study Evaluates Clinical Utility of Novel Liquid Biopsy-Breast Cancer Methylation Prototype Assay

A novel, automated liquid biopsy test—the Liquid Biopsy for Breast Cancer Methylation assay—may be effective at predicting early disease progression and potential survival outcomes in patients with metastatic breast cancer after as little as 1 month of treatment, according to a study published by...

Multiple Myeloma
Genomics/Genetics

Research Sheds Light on the Evolution of Precursor Conditions to Multiple Myeloma

Researchers have shared novel insights into the evolution of multiple myeloma from precursor disease, which may help physicians better identify patients whose disease is likely to progress as well as develop new interventions, according to a recent study published by Dang et al in Cancer Cell. How...

Solid Tumors
Genomics/Genetics

Adagrasib in Treatment of KRAS G12C–Mutated Advanced Solid Tumors

As reported in the Journal of Clinical Oncology by Tanios S. Bekaii-Saab, MD, and colleagues, findings in the phase II cohort of the KRYSTAL-1 trial showed activity of adagrasib in patients with KRAS G12C–mutated advanced solid tumors. As noted by the investigators, the KRAS G12C inhibitor...

Skin Cancer
Genomics/Genetics

Personalized mRNA Vaccines May Transform the Treatment of Melanoma

The rates of survival and disease recurrence improved significantly when a personalized mRNA vaccine tailored to the patients’ tumor genetics was coupled with immunotherapy in those who had undergone surgery for high-risk melanoma, according to novel findings presented by Khattak et al at the 2023...

Leukemia
Genomics/Genetics

Exposure to Ultraviolet Radiation May Propel Transformation of BPDCN Cells to Leukemia in the Skin

For some precancerous cells, traveling from the bone marrow to the skin can trigger genetic transformations that can result in leukemia, according to a novel study published by Griffin et al in Nature. The new findings may have shed light on what researchers have termed the “genetic travelogue” of...

lung cancer
genomics/genetics

Narjust Florez, MD, and Ferdinandos Skoulidis, MD, PhD, on NSCLC: Findings on Sotorasib vs Docetaxel in the CodeBreaK 200 Trial

Narjust Florez, MD, of Dana-Farber Cancer Institute, and Ferdinandos Skoulidis, MD, PhD, of The University of Texas MD Anderson Cancer Center, discuss results of a biomarker subgroup analysis, showing that sotorasib demonstrated consistent clinical benefit vs docetaxel in all molecularly defined subgroups of patients with pretreated KRAS G12C–mutated advanced non–small cell lung cancer (NSCLC). Although no predictive biomarkers were confirmed, novel hypothesis-generating signals were observed (Abstract 9008).

Solid Tumors
Genomics/Genetics

NCI’s ComboMATCH Initiative Will Evaluate New Drug Combinations Guided by Tumor Biology

The National Cancer Institute (NCI) has launched a new set of large, precision medicine–based clinical trials—known as the ComboMATCH initiative—that will examine the efficacy of novel drug combinations targeting specific tumor mutations in adult and pediatric patients with cancer. The new...

Genomics/Genetics
Survivorship

Anthracycline-Related Cardiomyopathy and HP Gene Expression in Childhood Cancer Survivors

In a study reported in JACC: CardioOncology, Singh et al found that haptoglobin (HP) gene expression was associated with risk of anthracycline-related cardiomyopathy in childhood cancer survivors. Study Details In the study, messenger RNA sequencing was performed on total RNA from the peripheral...

Genomics/Genetics
Solid Tumors
Bladder Cancer

Erdafitinib Achieves Responses Across Multiple Cancer Types With FGFR Alterations

Three clinical trials demonstrated positive results from the targeted therapy erdafitinib for patients with multiple tumor types harboring FGFR alterations. The data were presented at the 2023 ASCO Annual Meeting. Erdafitinib is an oral medication that blocks the activity of FGFR signaling...

CNS Cancers
Genomics/Genetics

Vorasidenib Delays Disease Progression or Death in Patients With Grade 2 IDH-Mutated Glioma

Vorasidenib, an oral dual inhibitor of mutant IDH1/2 enzymes, significantly improved progression-free survival in patients with grade 2 gliomas. This treatment delayed disease progression and was well tolerated. These findings from the INDIGO trial represent a significant step forward in the...

Lung Cancer
Genomics/Genetics

Adjuvant Osimertinib Improves Survival in Patients With Resected EGFR-Mutated NSCLC

Treatment with osimertinib after surgery significantly lowered the risk of death in adults with completely resected EGFR-mutated stage IB, II, or IIIA non–small cell lung cancer (NSCLC), according to the findings of the international ADAURA study. The research was presented at the 2023 ASCO Annual...

Lung Cancer
Genomics/Genetics

Patients With SLFN11-Expressing SCLC May Benefit From Immune Checkpoint Inhibitor Plus PARP Inhibitor

Among patients with extensive-stage small cell lung cancer (SCLC) positive for expression of the Schlafen-11 gene (SLFN11), those who received maintenance treatment with the immune checkpoint inhibitor atezolizumab plus the PARP inhibitor talazoparib had significantly longer progression-free...

Multiple Myeloma
Genomics/Genetics

CRISPR Approach May Help Identify Therapeutic Targets in Patients With Multiple Myeloma

Researchers have identified 116 genes as key molecular vulnerabilities for multiple myeloma, according to a novel study published by de Matos Simoes et al in Nature Cancer. The findings demonstrated the potential for these genes to act as leads and help researchers discover new therapeutic options...

Solid Tumors
Genomics/Genetics

Tumor Genomic Profile and Risk for Arterial Thromboembolism in Patients With Solid Cancer

  In a single-institution study reported in JACC: CardioOncology, Stephanie Feldman, MD, of Memorial Sloan Kettering Cancer Center, and colleagues found that somatic KRAS and STK11 alterations were associated with increased risk of arterial thromboembolism in patients with solid tumors,...

Genomics/Genetics

Genetic Sequencing May Identify Cancers Often Missed by Traditional Screening Guidelines

Whole-exome sequencing of a large database identified carriers of mutations associated with hereditary cancer syndromes (ie, hereditary breast and ovarian cancers and Lynch syndrome). What was surprising was that among those carriers, about 40% did not satisfy the existing National Comprehensive...

Colorectal Cancer
Genomics/Genetics
Immunotherapy

Addition of Panitumumab to Trifluridine/Tipiracil in Anti-EGFR Treatment Rechallenge in Refractory RAS Wild-Type Metastatic Colorectal Cancer

In the Italian phase II VELO trial reported in JAMA Oncology, Napolitano et al found that anti-EGFR treatment rechallenge with the addition of panitumumab to trifluridine/tipiracil improved progression-free survival in the third-line setting for patients with RAS wild-type metastatic colorectal...

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