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Bladder Cancer
Genomics/Genetics
Immunotherapy

Phase II Trial of Guadecitabine Plus Atezolizumab in Patients With Metastatic Bladder Cancer

Although hypomethylating agents previously appeared to be a promising treatment option for patients with bladder cancer refractory to immunotherapy, researchers were forced to halt a recent phase II clinical trial after patients experienced either no response to treatment or rapid tumor...

Breast Cancer
Colorectal Cancer
Prostate Cancer
Genomics/Genetics

Potential Utility of Polygenic Risk Scores in Cancer Screening in the United Kingdom

In a modeling study reported in The Lancet Oncology, Huntley et al found that the extension of UK cancer screening programs for breast, prostate, and colorectal cancers to a polygenic risk score (PRS)-defined high-risk group of patients with cancer may improve cancer case detection and avoidance of ...

Solid Tumors
Hematologic Malignancies
Genomics/Genetics

Familial Clonal Hematopoiesis in Individuals With a Mutation in Telomere-Related Gene POT1

In a study reported in The New England Journal of Medicine, DeBoy et al found that individuals carrying germline heterozygous loss-of-function mutations in the telomere-related gene POT1 had long telomeres and may be at risk for benign and malignant neoplasms as part of a familial clonal...

Lung Cancer
Genomics/Genetics

Sotorasib in Pretreated Patients With KRAS G12C–Mutated NSCLC: 2-Year Analysis of CodeBreaK100

In an analysis published in the Journal of Clinical Oncology, Grace K. Dy, MD, and colleagues report 2-year outcomes of the CodeBreaK100 phase I/II trial of sotorasib in previously treated patients with KRAS G12C–mutated locally advanced or metastatic non–small cell lung cancer (NSCLC). According...

Leukemia
Genomics/Genetics

Addition of Blinatumomab to Chemotherapy in Infant Patients With KMT2A-Rearranged ALL

In a phase II trial reported in The New England Journal of Medicine, van der Sluis et al found that the addition of blinatumomab—a bispecific T-cell engager molecule targeting CD19—to standard chemotherapy appeared to result in marked improvements in outcome among infants with KMT2A-rearranged...

Skin Cancer
Genomics/Genetics

Researchers Study Genetic Changes Across Multiple Organs of Metastatic Melanoma

Researchers have found that studying the landscape of DNA and RNA alterations across multiple organs of metastasis may provide a new direction in cancer therapeutics to address treatment failure, according to a new study published by Liu et al in Nature Medicine. The new findings from analyzing...

Breast Cancer
Genomics/Genetics

TONSL Gene May Be Potential New Target for Breast Cancer Therapy

Researchers may have discovered a new therapeutic target for patients with breast cancer—the TONSL gene—while attempting to understand the mechanisms behind breast cancer cell pathogenesis, according to a novel study published by Khatpe et al in Cancer Research. “Most of the cancer research to date ...

Solid Tumors
Genomics/Genetics

KRYSTAL-1 Update: Adagrasib Yields Benefit in Variety of KRAS G12C–Mutated Tumors

In the phase I/II KRYSTAL-1 trial, the KRAS inhibitor adagrasib demonstrated promising clinical activity in previously treated patients with pancreatic ductal adenocarcinoma, biliary tract cancer, and other solid tumors harboring KRAS G12C mutations, according to research presented at the April...

Solid Tumors
Genomics/Genetics

Early Trial Results Show Potential Benefits of FGFR Inhibitors and PARP/ATR Inhibitor Combinations in Multiple Tumor Types

In three new clinical trials, researchers have found that the novel fibroblast growth factor receptor (FGFR) inhibitor pemigatinib and new poly (ADP ribose) polymerase (PARP)/ataxia telangiectasia and Rad3-related (ATR) inhibitor combinations may be effective at treating patients with multiple...

Lung Cancer
Genomics/Genetics

Study Identifies Mutations That May Be Associated With Poor Outcomes in Patients With NSCLC Treated With KRAS G12C Inhibitors

Researchers have discovered that co-occurring mutations in three tumor-suppressor genes—KEAP1, SMARCA4, and CDKN2A—may be linked with poor clinical outcomes in patients with KRAS G12C–mutant non–small cell lung cancer (NSCLC) who were treated with the KRAS G12C inhibitors adagrasib or sotorasib,...

Solid Tumors
Supportive Care
Genomics/Genetics

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

In a single-institution study reported in JACC: CardioOncology, Feldman et al found that somatic KRAS and STK11 alterations were associated with increased risk of arterial thromboembolism in patients with solid tumors, irrespective of tumor type. Study Details The retrospective cohort study used...

Breast Cancer
Gynecologic Cancers
Colorectal Cancer
Genomics/Genetics

Whole-Exome Sequencing May Help Identify Individuals With Cancer Predisposition Syndromes Missed by Current Screening Guidelines

Researchers revealed that 39.2% of patients who consented to whole-exome sequencing and were identified as carriers of predisposition genes for hereditary breast and ovarian cancer or Lynch syndrome did not qualify for genetic screening under current guidelines, according to new findings presented...

Solid Tumors
Genomics/Genetics

Olaparib Plus Ceralasertib May Benefit Pediatric Patients With Cancer Who Have DNA Replication and/or Damage Repair–Deficient Tumors

Researchers have found that a combination of the PARP inhibitor olaparib and the investigational ATR inhibitor ceralasertib showed clinical benefit in pediatric patients with solid tumors exhibiting DNA replication and/or damage repair deficiencies, according to new findings presented by Gatz et al ...

Issues in Oncology
Genomics/Genetics

Liquid Biopsy–Based Multicancer Early Detection Test May Find Early-Stage and Low DNA–Shedding Cancers

Although plasma cell-free DNA (cfDNA) tests represent a promising approach for cancer screening, different methodologies vary in performance and many liquid biopsy tests show decreased performance in detecting early-stage or low-shedding DNA tumors. However, the results from a retrospective...

Colorectal Cancer
Genomics/Genetics
Issues in Oncology

Study Explores Genomic Basis of Racial Disparities Among Patients With Colorectal Cancer

Black individuals are disproportionately affected by colorectal cancer. They have the highest rates of the disease of any racial or ethnic group in the United States, and are about 20% more likely to develop colorectal cancer and about 40% more likely to die of the disease than most other groups. A ...

Genomics/Genetics
Geriatric Oncology

Cancer Susceptibility Germline Pathogenic Variants Among Older Patients

Hereditary cancer syndromes are caused by a pathogenic variant in cancer susceptibility genes, which overall account for approximately 10% of all cancers. Carriers of pathogenic variants are at an increased risk of developing cancer during their lifetime. Genomic cancer risk assessment makes it...

Colorectal Cancer
Genomics/Genetics

Consensus Molecular Subtypes as Markers for Maintenance Therapy Regimens for RAS Wild-Type Metastatic Colorectal Cancer

In an analysis of the German phase II PanaMa trial reported in the Journal of Clinical Oncology, Stahler et al evaluated consensus molecular subtypes as prognostic and predictive biomarkers in patients with RAS wild-type metastatic colorectal cancer receiving fluorouracil and leucovorin with or...

Leukemia
Genomics/Genetics

Combination Therapy May Help Patients With KMT2A-Mutated ALL or AML Overcome BET Inhibitor Resistance

Researchers have developed a novel combination therapy approach to help patients with KMT2A-mutated acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) overcome resistance to bromodomain and extraterminal domain (BET) inhibitors without adding toxicity, according to a novel study...

Gastrointestinal Cancer
Genomics/Genetics

Endoscopic Surveillance in Patients at Risk for Hereditary Diffuse Gastric Cancer

In a prospective cohort study reported in The Lancet Oncology, Asif et al found that endoscopic surveillance may be an alternative to prophylactic total gastrectomy in patients at risk for hereditary diffuse gastric cancer due to germline CDH1 pathogenic variants. Study Details In the study, 270...

Gastrointestinal Cancer
Genomics/Genetics

Interaction of H pylori Infection and Germline Pathogenic Variants in Risk for Gastric Cancer

In a Japanese study reported in The New England Journal of Medicine, Usui et al found that Helicobacter pylori infection affected the risk of gastric cancer in patients with predisposing germline pathogenic variants, including variants in homologous recombination genes. As stated by the...

Lung Cancer
Genomics/Genetics
Immunotherapy

ELCC 2023: New Data on Amivantamab-vmjw in Patients With Advanced NSCLC and EGFR Exon 20 Insertion Mutations

New long-term data from the CHRYSALIS study evaluating amivantamab-vmjw in patients with advanced non–small cell lung cancer (NSCLC) and EGFR exon 20 insertion mutations whose disease progressed on prior platinum-based chemotherapy were presented by Lopez et al at the 2023 European Lung Cancer...

Prostate Cancer
Genomics/Genetics

Addition of Niraparib to Abiraterone Acetate and Prednisone for Patients With Metastatic Castration-Resistant Prostate Cancer

As reported in the Journal of Clinical Oncology by Kim N. Chi, MD, and colleagues, the phase III MAGNITUDE trial showed that the addition of niraparib to abiraterone acetate and prednisone improved radiographic progression–free survival as first-line treatment in patients with metastatic...

Hepatobiliary Cancer
Genomics/Genetics

Hypercalcemia in Patients With Cholangiocarcinoma

In a study reported in a research letter in JAMA Oncology, Konstantinidou et al found that the prevalence of hypercalcemia increased over time in patients with cholangiocarcinoma and was significantly more common in those with IDH1-mutant intrahepatic disease. Study Details The study involved...

Skin Cancer
Genomics/Genetics

Researchers Uncover How Advanced Melanoma May Resist Treatment at the End of Life

Researchers have revealed the potential mechanisms contributing to treatment resistance in patients with melanoma at the end of life, according to a new study published by Spain et al in Cancer Discovery. “These results present the most detailed picture yet of what melanoma looks like at the final...

Bladder Cancer
Immunotherapy
Genomics/Genetics

How Do Novel Genetic Subtypes of Urothelial Carcinoma Respond to Immune Checkpoint Blockade?

In a study reported in the Journal of Clinical Oncology, Sarfaty et al identified novel genetic subtypes of urothelial carcinoma exhibiting different responses to immune checkpoint blockade. Study Details In the multicenter study, whole-exome sequencing was performed on tumor specimens from 88...

Skin Cancer
Genomics/Genetics

Naporafenib Plus Trametinib in Advanced NRAS-Mutant Melanoma

As reported in the Journal of Clinical Oncology by de Braud et al, findings in the expansion cohort of a phase Ib trial indicate activity with the combination of the BRAF/CRAF kinase inhibitor naporafenib and trametinib in patients with advanced or metastatic NRAS-mutant melanoma. Study Details In ...

Breast Cancer
Genomics/Genetics

Obesity May Contribute to Breast Cancer Risk in High-Risk Patients With BRCA Mutations

Obesity may spur DNA damage in the breast tissue of patients who carry BRCA1 or BRCA2 mutations, possibly contributing to breast cancer development in patients who are already at a higher risk of the disease, according to a new study published by Bhardwaj et al in Science Translational Medicine....

Lung Cancer
Genomics/Genetics

Sotorasib Improves Progression-Free Survival vs Docetaxel in Previously Treated Advanced NSCLC With KRAS G12C Mutation

As reported in The Lancet by ­Adrianus Johannes de Langen, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, and colleagues, the phase III CodeBreaK200 trial has shown a small but significant improvement in progression-free survival with sotorasib vs docetaxel in previously treated advanced...

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...

colorectal cancer
genomics/genetics

BRAF V600E–Mutated Colon Cancer

This is Part 2 of The Evolving Targeted Treatment Landscape for Colorectal Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable.   In this video, Drs. John Strickler, Stacey A. Cohen, and Harshabad Singh discuss the management of BRAF V600E–mutated colorectal cancer. The patient is a 40-year-old woman who presents to the ER with severe abdominal pain. CT scan of the chest, abdomen, and pelvis reveals a cecal mass with adjacent nodularity, abdominal lymphadenopathy, and multiple liver lesions consistent with metastatic disease. Colonoscopy demonstrates a nonobstructing mass in the ascending colon; pathology confirms adenocarcinoma, and biopsy of liver lesion confirms adenocarcinoma consistent with colorectal primary. Her performance status is limited due to severe abdominal pain related to her metastatic disease. The patient is started on FOLFOX plus bevacizumab, which results in an improvement in her pain and performance status. Next-generation sequencing reveals APC, SMAD4, and TP53 mutations, as well as a BRAF V600E mutation.   The faculty discuss the treatment options for patients with aggressive BRAF V600E mutations, which are associated with poor prognosis and EGFR resistance, in both the first- and second-line setting. They also highlight importance of individualizing treatment based on a patient’s age, performance status, goals of treatment, and comorbidities.

Leukemia
Genomics/Genetics

Study Reveals Potential Cause of Resistance to Revumenib in Patients With Acute Myeloid Leukemia

Use of the novel menin inhibitor revumenib has led to remissions in patients with acute myeloid leukemia (AML), and associated findings have suggested the mechanisms through which cancer cells may become resistant to such treatment, according to two studies published by Issa et al and Perner et al, ...

Bladder Cancer
Genomics/Genetics

Novel Urine Test May Play a Role in Bladder Cancer Prediction

Testing for genetic mutations in urine may help clinicians detect bladder cancer years before the disease shows clinical symptoms, according to new findings presented by Le Calvez-Kelm et al at the 2023 European Association of Urology Annual Congress (Abstract A0268). The researchers identified...

Breast Cancer
Gynecologic Cancers
Genomics/Genetics

Prevalence of High-Grade Serous Carcinoma at Risk-Reducing Salpingo-Oophorectomy in Asymptomatic Patients With BRCA1/2 Pathogenic Variants

In a Dutch study reported in the Journal of Clinical Oncology, Stroot et al identified the prevalence of high-grade serous carcinoma at risk-reducing salpingo-oophorectomy in asymptomatic BRCA1/2 pathogenic variant carriers. Study Details The study included asymptomatic BRCA1/2 pathogenic variant...

Breast Cancer
Gynecologic Cancers
Genomics/Genetics

Remote Interventions to Improve Uptake of Cancer Genetic Risk Assessment in Patients With Ovarian Cancer or High-Risk Breast Cancer

In a study reported in the Journal of Clinical Oncology, Anita Y. Kinney, PhD, RN, and colleagues found that a phone-based tailored risk counseling and navigation intervention resulted in a higher proportion of patients with ovarian or high-risk breast cancers receiving cancer genetic risk...

Gastrointestinal Cancer
Genomics/Genetics

Expert Point of View: Breelyn A. Wilky, MD

Discussant of the INTRIGUE abstract, Breelyn A. Wilky, MD, Director of Sarcoma Medical Oncology, Deputy Associate Director for Clinical Research, University of Colorado, Aurora, called the data presented “compelling evidence of the power of ctDNA [circulating tumor DNA] to identify predictive...

Gastrointestinal Cancer
Genomics/Genetics

INTRIGUE Study: Circulating Tumor DNA Analysis May Predict Optimal Treatment of Patients With GIST

Circulating tumor DNA (ctDNA) analysis of KIT exon mutations may help to predict which second-line therapy is best for patients with advanced gastrointestinal stromal tumor (GIST), according to data presented during the ASCO Plenary Series: January 2023 Session.1 Exploratory analysis of the phase...

Lymphoma
Genomics/Genetics

Whole-Genome Sequencing May Illuminate the Genetic Evolution of Classical Hodgkin Lymphoma

Researchers have discovered that whole-genome sequencing—rather than the current standard of exome sequencing—may allow physicians to better identify genetic changes that drive cancer development and growth, and create the most effective, personalized treatment plans for patients with classical...

Colorectal Cancer
Genomics/Genetics

KRYSTAL-1 Confirms Activity of Adagrasib in KRAS G12C–Mutated Metastatic Colorectal Cancer and Highlights Need for Randomized Controlled Trials

KRAS G12C–mutated colorectal cancer represents 3% to 4% of metastatic colorectal cancers. Like other KRAS-mutated metastatic colorectal cancers, this group of patients represents a patient population with an unmet need, with limited options beyond two lines of therapy. In contrast to other KRAS...

Colorectal Cancer
Genomics/Genetics

Adagrasib With or Without Cetuximab in Previously Treated Patients With Metastatic Colorectal Cancer and a KRAS G12C Mutation

In a phase I/II trial (KRYSTAL-1) reported in The New England Journal of Medicine, Rona Yaeger, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues found that the KRAS G12C inhibitor adagrasib showed activity alone and in combination with cetuximab in heavily pretreated patients ...

Genomics/Genetics
Survivorship

Higher Rate of Clonal Hematopoiesis in Pediatric Cancer Survivors May Be Linked With Treatment-Induced STAT3 Gene Mutations and Risk of Adverse Long-Term Outcomes

Studies show that although clonal hematopoiesis is an age-related phenomenon in the general population, it can also be induced by exposure to chemotherapy, which can affect both the emergence and evolution of clonal hematopoiesis clones, accelerating aging at both the physiologic and molecular...

Sarcoma
Genomics/Genetics

ctDNA as a Prognostic Marker in Intermediate-Risk Rhabdomyosarcoma

In a study from the Children’s Oncology Group reported in the Journal of Clinical Oncology, Abbou et al found that measuring circulating tumor DNA (ctDNA) in intermediate-risk rhabdomyosarcoma was feasible and that the presence of ctDNA prior to treatment was associated with poorer prognosis. As...

Lung Cancer
Genomics/Genetics

Adjuvant Osimertinib Significantly Improves Disease-Free Survival for Patients With Resected EGFR-Mutant NSCLC

The EGFR tyrosine kinase inhibitor osimertinib may improve rates of disease-free survival and reduce the risk of recurrence in patients with resected, EGFR­-mutant non–small cell lung cancer (NSCLC), according to a new exploratory analysis of the ADAURA trial published by Roy S. Herbst, MD, PhD,...

Issues in Oncology
Genomics/Genetics

Trends in Use of Next-Generation Sequencing in U.S. Patients According to Genetic Ancestry

In a study reported in a letter to the editor in The New England Journal of Medicine, Mata et al found that U.S. individuals of African ancestry and Hispanic patients made up an increasing proportion of patients undergoing next-generation sequencing of tumor samples over a 9-year period ending in...

Gastrointestinal Cancer
Genomics/Genetics
Immunotherapy

Analysis of Mutations Associated With High Tumor Mutation Burden in Microsatellite-Stable Gastrointestinal Cancers

In a study reported in The Lancet Oncology, Wang et al identified mutations linked to high tumor mutation burden in microsatellite-stable (MSS) gastrointestinal cancers that may be associated with efficacy of immune checkpoint inhibitor therapy. Study Details Molecular alterations in 48,606...

Skin Cancer
Genomics/Genetics
Immunotherapy

Study Explores the Addition of First-Line Atezolizumab in BRAF V600–Mutant Advanced Melanoma

As reported in The Lancet Oncology by Paolo A. Ascierto, MD, of the Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Pascale, Naples, and colleagues, the second interim overall survival analysis of the phase III IMspire150 trial has shown a numeric but...

Breast Cancer
Genomics/Genetics

Risk of Contralateral Breast Cancer Among Patients With Invasive Breast Cancer and Various Germline Pathogenic Variants

In a study reported in the Journal of Clinical Oncology, Yadav et al estimated the risk of contralateral breast cancer among patients with invasive breast cancer and germline pathogenic variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2. Study Details The study population consisted of 15,104...

Gastrointestinal Cancer
Genomics/Genetics

Molecular Tumor Board Offers Assistance That May Boost Effectiveness of Precision Oncology

The field of precision oncology has become so complex that even experienced oncologists can find it challenging to decipher the molecular test results of tumor tissue and navigate treatment options for patients. Investigators revealed that a new program may aid gastrointestinal cancer physicians in ...

Breast Cancer
Genomics/Genetics

Genomic Profile to Identify Candidates for Omission of Local Adjuvant Radiation Among Patients With Breast Cancer

In a study reported in the Journal of Clinical Oncology, Sjöström et al identified a 16-gene signature—Profile for the Omission of Local Adjuvant Radiation, or POLAR—that predicted low likelihood of benefit from adjuvant radiotherapy in preventing locoregional recurrence in patients with...

Solid Tumors
Lung Cancer
Genomics/Genetics

FoundationOne Liquid CDx Receives FDA Approval as a Companion Diagnostic for Entrectinib

On January 4, the U.S. Food and Drug Administration (FDA) approved FoundationOne Liquid CDx to be used as a companion diagnostic to identify patients with ROS1-positive non–small cell lung cancer (NSCLC) or NTRK fusion–positive solid tumors who do not have a tissue sample available and may be...

Breast Cancer
Genomics/Genetics

Risk Prediction Model for Contralateral Breast Cancer in BRCA Carriers With Breast Cancer

In a Chinese study reported in the Journal of Clinical Oncology, Sun et al developed a risk prediction model (BRCA-CRisk) to assess the risk of contralateral breast cancer in patients with breast cancer and BRCA1/2 pathogenic/likely pathogenic variants.  Study Details The model was developed in a...

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