Role of Inherited GATA3 Variant in Response to Treatment, Disease Relapse in Pediatric ALL
Research published by Zhang et al in the Journal of the National Cancer Institute showed that an inherited variation in the GATA3 gene strongly influences early response to chemotherapy and is linked to relapse in children with acute lymphoblastic leukemia (ALL). Minimal residual disease (MRD)...
Racial Differences in Genomic Profiles of Primary and Metastatic Prostate Cancer
In a letter to the editor published in The New England Journal of Medicine, Brandon A. Mahal, MD, and colleagues described genomic differences in prostate cancer in Black, White, and Asian men. Study Details The study involved next-generation sequencing data from patients who had been treated for...
Phase II Trial of Capmatinib for MET Exon 14–Mutated or MET-Amplified Advanced NSCLC
As reported in The New England Journal of Medicine by Wolf et al, the phase II GEOMETRY mono-1 trial has shown durable responses with the selective MET inhibitor capmatinib in patients with advanced non–small cell lung cancer (NSCLC) and MET exon 14–skipping mutations. The trial supported the May...
At Last: Targeting KRAS-Mutated Tumors ‘Is Now a Reality’
KRAS G12C inhibitors—which at this point include AMG 510 (now labeled sotorasib) and MRTX849—are proving to be active in KRAS G12C–mutated tumors, especially non–small cell lung cancer (NSCLC). KRAS G12C is a newly “druggable” target, joining what is still a limited list of some 3,000 potential...
PORTEC-3: Effect of Molecular Classification of Endometrial Cancer on Outcomes With Adjuvant Therapy
In a study reported in the Journal of Clinical Oncology, Alicia Léon-Castillo, MD, of Leiden University Medical Center, the Netherlands, and colleagues identified outcomes associated with molecular subgroups of patients with high-risk endometrial cancer enrolled in the PORTEC-3 trial of adjuvant...
FDA Approves FoundationOne Liquid CDx, a Pan-Tumor Liquid Biopsy Test
On August 28, the U.S. Food and Drug Administration (FDA) approved FoundationOne Liquid CDx, a comprehensive pan-tumor liquid biopsy test for patients with solid tumors. FoundationOne Liquid CDx is a comprehensive genomic-profiling test that analyzes more than 300 cancer-related genes and multiple...
Three Novel Genetic Variants Linked to Male Breast Cancer Discovered
Scientists have newly discovered three genetic changes that increase the risk of breast cancer in men. These findings were published by Maguire et al in the Journal of the National Cancer Institute. The researchers identified three common variations in DNA that predispose men to developing breast...
Dabrafenib Plus Trametinib in BRAF V600E–Mutated Tumors: NCI-MATCH Subprotocol H
As reported in the Journal of Clinical Oncology by Salama et al, the NCI-MATCH trial subprotocol H (EAY131-H) has shown durable responses with dabrafenib plus trametinib in previously treated patients with BRAF V600E–mutant tumors. Study Details The study enrolled 35 patients with mixed-histology...
Molecular Testing in Metastatic Colorectal Cancer: Understanding How, When, and What to Profile
“In line with the emergence of targeted therapies, molecular biomarker testing in metastatic colorectal cancer has evolved over the past decade,” noted Jeanne Tie, MD, MBChB, FRACP, who acknowledged there is confusion about the best ways to use molecular testing in the clinic. Dr. Tie, who is...
FDA Pipeline: Approval for First Liquid Biopsy Next-Generation Sequencing Companion Diagnostic; Designations in Ovarian Cancer, Leukemia, and Lymphoma
Recently, the U.S. Food and Drug Administration (FDA) approved the first liquid biopsy companion diagnostic that also uses next-generation sequencing technology to identify patients with non–small cell lung cancer (NSCLC) and specific types of EGFR mutations. The FDA also granted Fast Track...
CICERO Software May Enable Detection of Cancer-Causing Gene Fusions
After years of development, engineering, and enhancement, researchers at St. Jude Children’s Research Hospital in Memphis have made available a software system that enables better detection of gene fusions. The system, called CICERO, offers additional insights into cancers as well as new targets...
Higher Prevalence of Germline Mutations Identified in Young Adults With Cancer
A new study has found that a higher-than-expected proportion of young adults with cancer harbor genetic germline mutations that have implications for treatment, surveillance, and other family members who may be at risk. Patients with “early-onset cancers”—cancers that typically do not occur in...
NTRK Fusions in Gastrointestinal Cancers: Rare but Responsive to Treatment
Although NTRK gene fusions occur in less than 5% of gastrointestinal cancers, it looks like they can be targeted successfully with NTRK inhibitors. In a pooled analysis of three clinical trials, 50% of such patients responded to entrectinib, in an updated analysis presented during the 2020 virtual...
Role of TP53 Mutations on Disease Severity in Myelodysplastic Syndromes
Considered the “guardian of the genome,” TP53 is the most commonly mutated gene in patients with cancer. TP53's normal function is to detect DNA damage and prevent cells from passing this damage on to daughter cells. When TP53 is mutated, the protein made from this gene, called p53, can no longer...
Analysis of Deep Whole-Genome Sequencing in Patients With Multiple Myeloma Identifies Superior Outcome Subgroup
In a study of genome-wide somatic alterations in multiple myeloma reported in the Journal of Clinical Oncology, Samur et al identified a subgroup of patients with superior outcomes who are not adequately identified by traditional risk markers. The study involved analysis of deep whole-genome...
Impact of Pregnancy After Breast Cancer in Women With Deleterious Germline BRCA Mutations
In a retrospective cohort study reported in the Journal of Clinical Oncology, Matteo Lambertini, MD, PhD, and colleagues found that pregnancy after breast cancer in women harboring deleterious germline BRCA mutations did not appear to be associated with worsened maternal prognosis or fetal...
Treatment of KRAS G12C Mutation
Drs. Ramalingam, Brahmer, and Wakelee review the role of KRAS G12C mutation in lung cancer, which is found is 13% of all non–small cell lung cancer. They highlight two investigational therapies, AMG 510 and MRTX 849, and discuss recently presented data.
Effect of Breast Cancer Pathway Implementation on Rate of Referrals for Genetic Counseling and Testing
In a study reported in JCO Oncology Practice, Stephanie L. Graff, MD, and colleagues found that patients with breast cancer seen by a physician with training in using an established pathway for genetic counseling and testing referral were more frequently referred for such services vs patients seen...
Presence of ctDNA and CTCs and Prediction of Disease Recurrence in Patients With Triple-Negative Breast Cancer
In a preplanned secondary analysis of the BRE12-158 trial published in JAMA Oncology, Milan Radovich, PhD, and colleagues found that the presence of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) in the plasma of women who have received neoadjuvant treatment for stage I, II, or...
Trends in Policy Coverage for ctDNA Testing
New research published by Douglas et al in JNCCN—Journal of the National Comprehensive Cancer Network examined coverage trends for circulating tumor DNA (ctDNA) testing, also known as liquid biopsy. In the first-ever study to analyze insurance coverage for ctDNA-based panel tests, researchers found ...
Study Finds Young Adults With Cancer May Harbor Germline Mutations and Benefit From Germline Genetic Testing
According to the National Cancer Institute, each year, about 70,000 adolescents and young adults (AYAs)—those between the ages of 15 and39—are diagnosed with cancer.1 Evidence suggests that some cancers found in AYAs may have unique genetic and biologic features. The findings of a recent study by...
New Recommendations Offer Guidance for Clinicians and Patients on Genetic Testing for Prostate Cancer
An international panel of experts led by researchers and thought leaders at the Sidney Kimmel Cancer Center–Jefferson Health (SKCC) and the Department of Urology at Jefferson have published the first multidisciplinary, consensus-driven, prostate cancer genetic implementation framework for the...
Variant in Gene May Increase Cancer Risk in Those With Common TP53 R337H Mutations
Scientists studying a common TP53 R337H variant found among people of Brazilian descent discovered that a variant in the tumor-suppressor gene XAF1 increases cancer risk when combined with the inherited TP53 R337H mutation. These findings were published by Pinto et al in Science Advances. “We...
Young Adults With Cancer May Benefit From Germline Genetic Testing
According to the National Cancer Institute, each year, about 70,000 adolescents and young adults (AYA)—those between the ages of 15 and 39—are diagnosed with cancer. Evidence suggests that some cancers found in AYA patients may have unique genetic and biologic features. A study that investigated...
FGFR1–3 Inhibitor AZD4547 in Refractory Tumors Harboring FGFR Activating Mutations and Fusions
As reported in the Journal of Clinical Oncology by Chae et al, findings in a cohort of the phase II NCI-MATCH trial (EAY131, Subprotocol W) indicated that the oral inhibitor of fibroblast growth factor receptor 1, 2, and 3 (FGFR1–3), AZD4547, produced a small number of responses in patients with a...
First-Line Platinum-Based Chemotherapy for Patients With Metastatic Pancreatic Cancer and Defects in Homologous Recombination Genes
Patients with metastatic pancreatic cancer who had germline or somatic mutations in DNA repair genes had better clinical outcomes after platinum-based chemotherapy compared to patients without these mutations, according to results from a study published by Park et al in Clinical Cancer Research....
Genomic Characteristics of Smoldering Multiple Myeloma and Risk of Progression
In a study reported in the Journal of Clinical Oncology, Mark Bustoros, MD, and colleagues identified genomic features of smoldering multiple myeloma associated with a higher risk of progression to multiple myeloma and found that alterations that drive disease progression are already present at the ...
RET Kinase Inhibitor for Patients With Solid Tumors and RET Genetic Fusions
The RET inhibitor pralsetinib showed activity in patients with a broad variety of tumors harboring RET gene fusions, according to results from the phase I/II ARROW trial, presented by Vivek Subbiah, MD, and colleagues during the ASCO20 Virtual Scientific Program (Abstract 109). “This trial shows...
Remote Pre- and Posttest Genetic Counseling for Breast and Ovarian Cancer Risk
Genetic testing for cancer risk can significantly improve the prevention or treatment of hereditary cancers, but studies have shown that people who might have a genetic risk often don't get tested. A collaborative team of researchers have tested a possible solution through a clinical trial aimed at ...
Precision Medicine Is Becoming a Reality for Pediatric Patients With Cancer
Although 84% of children with cancer survive 5 years or more, children with refractory, relapsed, and progressive high-risk malignancies have a poor median survival of 9.5 months. The German INFORM registry is a large prospective, noninterventional, multicenter study collecting clinical and...
How California Dreamer John Craig Venter, PhD, Changed Paths to Focus on Sequencing the Human Genome
In this edition of the Living a Full Life series, guest editor Jame Abraham, MD, FACP, spoke with John Craig Venter, PhD, Founder, Chairman, and Chief Executive Officer of the J. Craig Venter Institute, a nonprofit organization dedicated to human, microbial, and environmental genomic research. A...
Germline Genetic Variants in ATM and Lung Cancer Susceptibility
An international consortium of researchers has identified a mutation involved in a person’s susceptibility to lung cancer. This variant could help identify certain populations at greater risk for lung cancer, according to results reported by Ji et al in Nature Communications. ATM Variant Their...
FDA Approves Selpercatinib for Lung and Thyroid Cancers With RET Mutations or Fusions
On May 8, 2020, the U.S. Food and Drug Administration (FDA) granted accelerated approval to selpercatinib (Retevmo) for the following indications: Adult patients with metastatic RET fusion–positive non–small cell lung cancer (NSCLC) Adult and pediatric patients ≥ 12 years of age with advanced or...
Joint Guideline Sheds Light on Management of Hereditary Breast Cancer
As germline genetic testing becomes more widespread among patients with breast cancer, recommendations for the appropriate management of patients with hereditary breast cancer are needed. Until now, no ASCO guideline has addressed the management of hereditary breast cancer, even for carriers of...
AACR 2020: Cell-Free DNA Liquid Biopsy May Provide an Early Detection Test for Patients With Suspected Cancer
The Circulating Cell-free Genome Atlas Study is a large multicenter, case-controlled, observational study of 15,254 participants, 56% with cancer and 44% without cancer, with longitudinal follow-up to support the development of a cell-free DNA (cfDNA) multicancer early detection test. In this phase ...
How CRISPR-Cas9 Gene Editing May Improve the Effectiveness of Cellular Therapeutics in Patients With Cancer
The results from the first in-human phase I clinical trial in the United States evaluating CRISPR-Cas9–edited T cells in patients with advanced cancer has shown that the therapy is both feasible and safe, representing a big step forward in the potential of using gene editing to boost the natural...
Should Restrictions on Genetic Testing Be Loosened?
The loosening of restrictions on genetic testing would mean that all health-care providers could help move this needle to where it should be, according to Kevin S. Hughes, MD, a surgeon at Massachusetts General Hospital, Professor of Surgery at Harvard Medical School, and Medical Director of the...
Methylation Signatures From Sequencing Circulating Cell-Free DNA Detected Different Types of Cancer Across Multiple Stages
Researchers have developed the first blood test that can accurately detect more than 50 types of cancer and identify in which tissue the cancer originated—often before there are any clinical signs or symptoms of the disease. These findings were published by Liu et al in Annals of Oncology. In their ...
First-in-Human Study of RAF Family Kinase Inhibitor Lifirafenib in Solid Tumors
In a first-in-human phase I trial reported in the Journal of Clinical Oncology, Desai et al found that the RAF family kinase inhibitor lifirafenib produced responses in several solid tumor types in patients with BRAF or KRAS/NRAS mutations. Study Details The study, conducted in Australia and New...
International Uptake of Molecular Testing Across Tumor Types: Analysis of Eight Countries
In a study reported in JCO Oncology Practice, Chambers et al found that use of molecular testing across tumor types often varied widely in several countries, sometimes reflecting regional differences in the incidence of cancer types. Study Details The study involved the use of aggregated results of ...
Genetic Counseling and Testing of Patients With Pancreatic Cancer
Routine genetic counseling and multigene testing of patients with pancreatic cancer result in the detection of mutations that are actionable, not only for patients, but also for at-risk family members. At the Dana-Farber Cancer Institute in Boston, the use of a systemized, automated referral system ...
Association of Germline Variant Status and Response to Neoadjuvant Chemotherapy in High-Risk Early Breast Cancer
In a study of the GeparOcto trial population reported in JAMA Oncology, Pohl-Rescigno et al found that presence of germline BRCA1/2 variants was associated with increased rates of complete pathologic response (pCR) to neoadjuvant chemotherapy in women with high-risk early breast cancer, and that a...
Evaluation of Genetic Testing in NCCN Criteria for Women With Breast Cancer
In a single-institution study reported in the Journal of Clinical Oncology, Yadav et al found that many women with breast cancer with germline pathogenic genetic variants do not qualify for genetic testing on current National Comprehensive Cancer Network® (NCCN®) hereditary testing criteria....
Avapritinib for Gastrointestinal Stromal Tumor With PDGFRA Exon 18 Mutation
On January 9, 2020, avapritinib was approved for treatment of adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including D842V mutations.1,2 It is the first therapy approved for...
Geographic and Racial Variability in Germline BRCA Mutation Prevalence Among Patients With Metastatic Pancreatic Cancer
In a study reported in the Journal of Clinical Oncology, Talia Golan, MD, and colleagues identified geographic and ethnic heterogeneity of germline BRCA1/2 mutation prevalence among patients screened for entry into the phase III POLO trial, which examined the efficacy of olaparib maintenance...
Automated Referral Process for Genetic Counseling and Testing of Patients With Pancreatic Cancer
Routine genetic counseling and multigene testing of patients with pancreatic cancer result in the detection of mutations that are actionable, not only for patients, but also for at-risk family members. At the Dana-Farber Cancer Institute, the use of a systemized, automated referral system that does ...
New ASCO Guideline Highlights Need to Improve Germline, Somatic Tumor Testing in Epithelial Ovarian Cancer
A new ASCO clinical practice guideline provides clinicians and other health-care professionals with evidence-based recommendations on genetic and tumor testing for women diagnosed with epithelial ovarian cancer.1 “We wanted to go over the evidence and make strong statements and recommendations...
Neoadjuvant Cisplatin for BRCA-Mutation Carriers: Pruning the Dead Branches
At the 2019 San Antonio Breast Cancer Symposium, Nadine Tung, MD, of Beth Israel Deaconess Medical Center, presented a multisite study called INFORM, run by the Translational Breast Cancer Research Consortium.1 It compared single-agent cisplatin with a “classic” combination of doxorubicin and...
Genetic Mutations in Donor Stem Cells May Affect Hematopoietic Transplant Recipients
A new study on hematopoietic stem cell transplantation from Washington University School of Medicine in St. Louis suggests that extremely rare, harmful genetic mutations present in healthy donors’ stem cells—though not causing health problems in the donors—may be passed on to patients with cancer...
Study Finds Women With Variants in Breast Cancer–Associated Genes May Not Always Be Receiving Guideline-Concordant Care
Women with early-stage breast cancer who test positive for an inherited genetic variant are not always receiving cancer treatment that follows current treatment guidelines, according to findings from a new study published by Allison W. Kurian, MD, MSc, and colleagues in JAMA Oncology. An inherited ...
