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Genomics/Genetics

FDA Approves FoundationOne CDx as a Companion Diagnostic for Entrectinib

On June 9, Foundation Medicine, Inc., announced that it has received approval from the U.S. Food and Drug Administration (FDA) for FoundationOne CDx to be used as a companion diagnostic for the two indications of the tyrosine kinase inhibitor entrectinib (Rozlytrek). As a companion diagnostic,...

prostate cancer
genomics/genetics

Neal D. Shore, MD, on Germline Genetic Testing and Its Impact on Prostate Cancer Clinical Decision-Making

Neal D. Shore, MD, of the Carolina Urologic Research Center, discusses his study findings, showing that germline genetic testing influenced care for patients with prostate cancer. Men whose genetic test was positive for a pathogenic germline variant received more recommendations for changes to follow-up and treatment, and for testing and counseling of relatives, than did patients with negative or uncertain test results (Abstract 10500).  

Genomics/Genetics

Patient-Facing Screening Tool Could Increase Detection of Individuals With Lynch Syndrome

Nearly 1 million people in the United States are affected by Lynch syndrome, a hereditary cancer condition with markedly elevated risk of gastrointestinal, endometrial, and other cancers. Most of them, however, are unaware of it, or find out only after they have developed cancer. A screening...

Breast Cancer
Genomics/Genetics

Study Finds Genetic Mutations Differ Across Younger and Older Patients With Breast Cancer

Women younger than age 40 with advanced breast cancer often experience more aggressive disease and worse prognoses than their older counterparts. Knowing which types of genetic mutations these patients tend to have may inform treatment strategies and improve outcomes. In a recent study, researchers ...

Breast Cancer
Genomics/Genetics

Study Examines Ancestry-Specific Genetic Risk for Triple-Negative Breast Cancer

Although women of African descent experience a higher incidence and mortality from triple-negative breast cancer than women of other races or ethnicities, research findings presented by Hall et al at the 2022 ASCO Annual Meeting showed that the magnitude of gene-specific risks of triple-negative...

Cost of Care
Genomics/Genetics

New Study Assesses Oncologists’ Ratings of the Importance of Health Insurance and Costs for Genomic Testing

A new study led by researchers at the American Cancer Society showed physician, practice, and patient characteristics were associated with oncologists’ ratings of the importance of patient health insurance and out-of-pocket costs for genomic testing in treatment decisions. The findings are being...

Genomics/Genetics

Study Points to Expanded Genomic Testing to Benefit Children and Young Adults With Cancer

New findings from researchers at Memorial Sloan Kettering Cancer Center published by Shukla et al in Nature Communications reported the results of using a comprehensive sequencing approach on 114 pediatric, adolescent, and young adult patients with solid tumors. The researchers found that their...

lung cancer
genomics/genetics

Matthew L. Meyerson, MD, PhD, on Lung Adenocarcinoma: Somatic Mutations, Germline Risk, and Ancestry

Matthew L. Meyerson, MD, PhD, of the Dana-Farber Cancer Institute, discusses study findings that suggest the variation in frequency of EGFR and KRAS mutations in lung cancer may be associated with genetic ancestry in patients from Latin America. The results indicate it may be possible to identify germline alleles underpinning this link. Finding a germline locus or loci may impact the development of lung cancers with these mutations and may improve lung cancer prevention and screening for populations of Latin American origin, as well as others.

Bladder Cancer
Genomics/Genetics

Report Finds Uptake of Erdafitinib for Urothelial Cancer May Be Limited, Despite Positive Real-World Survival Data

The first bladder cancer drug targeting a cancer-driving gene mutation has been used relatively little despite its clear efficacy in a clinical trial, suggests a report published as a research letter by Nimgaonkar et al in JAMA Oncology. Researchers analyzed a large, nationwide database of cancer...

Solid Tumors
Genomics/Genetics

Next-Generation PARP1-Selective Inhibitor Offers Significant Benefits Over Older Predecessors in Treatment of Solid Tumors

The first-in-human, first-in-class trial of the next-generation PARP (poly [ADP-ribose] polymerase) 1–selective inhibitor AZD5305 suggests this drug may be a welcome advance over its U.S. Food and Drug Administration (FDA)-approved predecessors in the treatment of solid tumors with alterations in...

issues in oncology
genomics/genetics

Nickolas Papadopoulos, PhD, on Multicancer Early Detection: Opportunities and Challenges

Nickolas Papadopoulos, PhD, of the Sidney Kimmel Comprehensive Cancer Center, discusses early detection as the key to reducing cancer mortality and the lack of tests for many malignancies. Liquid biopsies have the potential to screen for various tumor types, albeit with varying levels of sensitivity. Dr. Papadopoulos discusses his research on such blood tests, following patients prospectively to find the best combination of genetic and epigenetic biomarkers to increase sensitivity (Abstract PL02).

Hepatobiliary Cancer
Pancreatic Cancer
Immunotherapy
Genomics/Genetics

Ipilimumab/Nivolumab in Patients With Metastatic Pancreatic or Biliary Cancer and HRD Pathogenic Germline Variants

In a single-institution case series reported in a research letter in JAMA Oncology, Terrero et al found that the combination of ipilimumab and nivolumab was active in patients with chemotherapy-refractory metastatic pancreatic or biliary cancer with homologous recombination deficiency (HRD)...

pancreatic cancer
genomics/genetics

Christine A. Iacobuzio-Donahue, MD, PhD, on Pancreatic Cancer: Novel Insights Into Genetics and Evolution

Christine A. Iacobuzio-Donahue, MD, PhD, of Memorial Sloan Kettering Cancer Center, discusses her research on the evolutionary features of advanced stage pancreatic cancers and the insights that may be used to help improve patient outcomes (Abstract PL05).

Lung Cancer
Genomics/Genetics
Immunotherapy

DESTINY-Lung01: Is Trastuzumab Deruxtecan the Answer for HER2-Mutant Lung Cancer?

The human epidermal growth factor (HER) family of receptors are a well-established therapeutic target. Indeed, seminal studies conducted nearly 2 decades ago identified a key association between activating mutations in the kinase domain of the epidermal growth factor receptor (EGFR, also known as...

Lung Cancer
Genomics/Genetics
Immunotherapy

DESTINY-Lung01: T-DXd Shows Durable Activity in Previously Treated Metastatic HER2-Mutant NSCLC

In a phase II trial (DESTINY-Lung01) reported in The New England Journal of Medicine, Bob T. Li, MD, PhD, MPH, of the Thoracic Oncology and Early Drug Development Service, Memorial Sloan Kettering Cancer Center, New York, and colleagues found that fam-trastuzumab deruxtecan-nxki (T-DXd) showed...

Genomics/Genetics

Association of Pathogenic Variants in Hereditary Cancer Genes With Additional Cancers and Non-neoplastic Diseases

In a study reported in JAMA Oncology, Zeng et al found that germline pathogenic variants in 23 hereditary cancer genes were associated with an increased risk of cancers not previously associated with the variants, as well as an increased risk of multiple non-neoplastic diseases. Study Details The...

issues in oncology
genomics/genetics

Charles L. Sawyers, MD, on Transforming Patient Outcomes: The Future of Cancer Research

Charles L. Sawyers, MD, of Memorial Sloan Kettering Cancer Center, discusses the battle against treatment resistance and how to overcome it, as well as the power of observational clinical data in precision oncology, derived largely from his experience with Project GENIE, and the role of genetic ancestry (Abstract PL02).

Gastroesophageal Cancer
Genomics/Genetics

Study Identifies Genetic Changes in Patients With Barrett’s Esophagus That Progresses to Esophageal Cancer

Using whole-genome sequencing to contrast genomic alterations in patients with stable Barrett’s esophagus compared to patients whose Barrett’s progressed to esophageal adenocarcinoma, Paulson et al reported that DNA changes presaging esophageal cancer can be spotted years before cancer develops....

issues in oncology
genomics/genetics

Priscilla K. Brastianos, MD, on CNS Metastases: Understanding Their Evolution and the Clinical Implications

Priscilla K. Brastianos, MD, of Harvard Medical School and Massachusetts General Hospital, talks about her efforts to better understand how brain metastases evolve genomically and to test such agents as abemaciclib, paxalisib, and entrectinib, which may stop their growth. Palbociclib, a CDK inhibitor, has already shown potential benefit. A national cooperative group trial is underway in multiple centers to identify novel treatments for patients with brain metastases, who typically have a poor prognosis (Abstract SY38).

gynecologic cancers
breast cancer
pancreatic cancer
prostate cancer
genomics/genetics

Timothy A. Yap, MBBS, PhD, on Ovarian, Breast, Pancreatic, and Prostate Cancers With Genetic Mutations: A First-in-Human Trial of AZD5305

Timothy A. Yap, MBBS, PhD, of The University of Texas MD Anderson Cancer Center, discusses results from the PETRA study, a first-in-class, first-in-human trial of the next-generation PARP1-selective inhibitor AZD5305 in patients with BRCA1/2, PALB2, or RAD51C/D mutations in advanced or metastatic ovarian cancer, HER2-negative breast cancer, pancreatic, or prostate cancer. Target engagement was demonstrated across all dose levels, and antitumor activity was observed in selected tumor and molecular subtypes.

Hepatobiliary Cancer
Gastroesophageal Cancer
Genomics/Genetics

Assessment of Cancer Risk Profile for Germline BRCA1 and BRCA2 Pathogenic Variants in Patients With Common Cancers

In a Japanese case-control study reported in JAMA Oncology, Momozawa et al found that germline BRCA1/2 pathogenic variants were associated with an increased risk of biliary tract, esophageal, and gastric cancers, in addition to an increased risk of cancers that have well-established associations...

prostate cancer
genomics/genetics

First-Line Therapy for BRCA2-Mutated Metastatic Castration-Resistant Prostate Cancer

This is Part 3 of Updates in Prostate Cancer, a four-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Celestia (Tia) Higano, Julie Graff, and Neal Shore discuss the first-line therapy for BRCA2-mutated metastatic castration-resistant prostate cancer. The patient is a 69-year-old man with new castration-resistant prostate cancer who was previously treated with androgen-deprivation therapy plus docetaxel for metastatic hormone-sensitive prostate cancer and has a known BRCA2 mutation. The faculty discuss their choices for first-line therapy for this patient, reviewing the current NCCN recommendations, the role of PARP inhibitors, and recent data from the PROpel and MAGNITUDE trials.

Genomics/Genetics

Maternal Malignancies May Be Identified Through Noninvasive Prenatal Test Results

In a Dutch study reported in the Journal of Clinical Oncology, Heesterbeek et al found that results of noninvasive prenatal testing for fetal aneuploidy screening using cell-free DNA derived from maternal plasma raised suspicion of maternal malignancy in a very small proportion of pregnant women....

genomics/genetics
issues in oncology

Cheryl L. Willman, MD, on Cancer Genomic Sequencing in Tribal Nations of the American Southwest

Cheryl L. Willman, MD, of the Mayo Clinic Comprehensive Cancer Center, discusses the profound cancer health disparities among Native Americans, exacerbated by low rates of screening and limited access to care. Dr. Willman is heading an effort to promote community engagement in comprehensive genomic sequencing with the hope that researchers will discover novel mutations and genome-wide mutational signatures that can ultimately be translated to improved screening and therapy in this population (Abstract PL03).

lung cancer
genomics/genetics

Jia Luo, MD, on NSCLC: Clinicopathologic and Molecular Characterization of KRAS G12D–Mutated Disease

Jia Luo, MD, of Dana-Farber Cancer Institute, discusses the emerging class of cancer therapies for allele-specific KRAS inhibitors and the importance of their distinct clinical, genomic, and immunologic features. Because KRAS G12D–mutated non–small cell lung cancer is associated with worse responses to immunotherapy, Dr. Luo believes drug development will need to take these differences into account (Abstract 4117).

Hematologic Malignancies
Genomics/Genetics

John Mascarenhas, MD, on the Implications of the FIGHT-203 Trial

John Mascarenhas, MD, Director of the Adult Leukemia Program at The Tisch Cancer Institute at Mount Sinai, New York, commented on the implications of the FIGHT-203 trial, which evaluated pemigatinib in myeloid or lymphoid neoplasms. Pemigatinib is an oral small-molecule receptor tyrosine kinase...

Hematologic Malignancies
Genomics/Genetics

Study Shows Pemigatinib Activity in Treatment of Myeloid or Lymphoid Neoplasms With FGFR1 Rearrangement

In patients with myeloid or lymphoid neoplasms with FGFR1 rearrangements, pemigatinib produced high and durable response rates, despite patients’ extensive use of prior treatments or hematopoietic stem cell transplantation (HSCT), according to the early results of the multicenter phase II FIGHT-203 ...

Solid Tumors
Genomics/Genetics

Selumetinib in Children and Young Adults With Tumors That Have Activating MAPK Pathway Alterations

In a phase II trial (arm E of the NCI-COG Pediatric MATCH trial) reported in the Journal of Clinical Oncology, Eckstein et al found that the MEK inhibitor selumetinib showed little activity in pediatric and young adult patients with tumors harboring activating MAPK pathway mutations or fusions. As...

Genomics/Genetics

Study Findings Broaden Repertoire of Cancer-Relevant Genes

Following an analysis of over 12,000 human genes, research from Yale Cancer Center indicates there is cancer-relevant importance in a much larger proportion of human genes than current cancer research models suggest. Much of cancer biology research focuses on a few dozen well-studied genes called...

Skin Cancer
Genomics/Genetics

Turnaround Times in Melanoma BRAF Testing and Effect on Time to Treatment Initiation

In a single-center study reported in JCO Oncology Practice, Ceballos et al identified turnaround times for request and receipt of melanoma BRAF testing results. They also analyzed factors in differences in turnaround times and effects on time to initiation of treatment. The study included 66...

Genomics/Genetics

New Bioinformatics Platform Optimizes Selection of Combination Cancer Therapies

Researchers at The University of Texas MD Anderson Cancer Center have developed a new bioinformatics platform that predicts optimal treatment combinations for a given group of patients based on co-occurring tumor alterations. In retrospective validation studies, the tool selected combinations that...

genomics/genetics

Patricia M. LoRusso, DO, on Targeting KRAS: Clinical Successes and Challenges

Patricia M. LoRusso, DO, of the Yale University School of Medicine, discusses how patients may benefit in the coming decade from discoveries about agents that target KRAS, and how important the approval of sotorasib turned out to be, as well as other agents in the research pipeline. Dr. LoRusso also talks about the scientific advances in tackling inhibition (Abstract SY20).

Lung Cancer
Genomics/Genetics
Immunotherapy

Patients With Lung Cancer and a Genetic Variant Linked to Autoimmune Disease May Be Especially Responsive to Immunotherapy

A variant of the CTLA-4 gene associated with autoimmune disease was found to be more frequent in patients with non–small cell lung cancer (NSCLC) who experienced an exceptionally high response to anti–PD-1 immunotherapy and a higher rate of immune-related side effects than in a comparable cohort of ...

Breast Cancer
Genomics/Genetics

Expert Point of View: Mark E. Robson, MD

“OlympiA is clearly a practice-changing trial, and olaparib should be offered to patients meeting the entry criteria for the study,” said Mark E. Robson, MD, Chief of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center, New York. Dr. Robson was invited to discuss the findings of...

Breast Cancer
Genomics/Genetics

OlympiA Trial: Adjuvant Olaparib Significantly Improves Overall Survival in Germline BRCA-Mutated Breast Cancer

The OlympiA trial of adjuvant olaparib in patients with HER2-negative, high-risk ­early-stage breast cancer and BRCA1 and BRCA2 mutations has now demonstrated a significant overall survival benefit, reducing the risk of death over placebo by 32% and yielding an absolute improvement of 3.8% at 3...

Genomics/Genetics

FDA Approves Alpelisib for PIK3CA-Related Overgrowth Spectrum

On April 5, the U.S. Food and Drug Administration (FDA) granted accelerated approval to alpelisib (Vijoice) for adult and pediatric patients aged 2 years and older with severe manifestations of PIK3CA-related overgrowth spectrum (PROS) who require systemic therapy. PROS encompasses a group of rare...

Thyroid Cancer
Genomics/Genetics

Expert Point of View: Alexander T. Pearson, MD, PhD

Alexander T. Pearson, MD, PhD, Assistant Professor of Medicine at the University of Chicago, commended the artificial intelligence (AI)-augmented, ultrasound-based platform for screening and staging of thyroid cancer.  “In this study, Dr. Chan and colleagues processed high-resolution ultrasound...

Thyroid Cancer
Genomics/Genetics

Study Finds AI Ultrasound Platform Can Predict Thyroid Malignancy, Pathologic Stage, and BRAF Mutation Status

An artificial intelligence (AI) ultrasound platform that incorporates multiple methods of machine learning can accurately predict thyroid malignancy as well as pathologic and genomic outcomes, according to data presented at the 2022 Multidisciplinary Head and Neck Cancers Symposium.1 Findings from...

leukemia
genomics/genetics

Therapy Options for Primary Refractory FLT3-ITD–Positive AML

In this video, Drs. Richard Stone, Courtney DiNardo, and Eunice Wang treatment options for primary refractory FLT3-ITD–positive acute myeloid leukemia (AML). The case is a 60-year-old man with a history of hypertension and hyperlipidemia who presents with fatigue. He is diagnosed with FLT3-ITD–positive AML and is enrolled in a clinical trial where he receives 7+3 (cytarabine/daunorubicin) and midostaurin; after achieving complete remission, his disease eventually recurs. The faculty discuss potential treatment options for this patient, such as FLAG-IDA-VEN and gilteritinib both alone and in combination.

leukemia
genomics/genetics

Induction Therapy for an Older Patient With IDH1-Mutant AML

In this video, Drs. Richard Stone, Courtney DiNardo, and Eunice Wang discuss the management of newly diagnosed older patients with acute myeloid leukemia (AML). The case is a 75-year-old woman with no past medical history who presents with fever and bone pain. She is diagnosed with AML, and next-generation sequencing reveals a mutation in IDH1, among others. The faculty discuss the potential choices for induction therapy in older patients such as this, debating the merits of intensive chemotherapy vs lower-intensity options such as azacitidine/venetoclax and azacitidine/ivosidenib.

Gynecologic Cancers
Genomics/Genetics

ARIEL4 Trial: Rucaparib vs Chemotherapy in Patients With Relapsed Ovarian Cancer and Deleterious BRCA1 or BRCA2 Mutations

As reported in The Lancet Oncology by Rebecca Kristeleit, MD, and colleagues, the phase III ARIEL4 trial has shown a statistically significant improvement in progression-free survival with rucaparib vs chemotherapy in patients with relapsed ovarian cancer and deleterious BRCA1/2 mutations. Study...

Genomics/Genetics

Results From MAPPYACTS Trial Show the Feasibility and Benefit of Molecular Profiling at Cancer Recurrence in Pediatric Patients

Despite advances in treatment for pediatric patients, cancer remains the primary cause of disease-related mortality in children and adolescents. Data from the international clinical trial MAPPYACTS, which aims to define tumor molecular profiles in pediatric patients with recurrent/refractory...

Pancreatic Cancer
Genomics/Genetics

Expert Point of View: E. Gabriela Chiorean, MD

The invited discussant of the CodeBreaK 100 data, E. Gabriela Chiorean, MD, Professor of Medicine at the University of Washington and Fred Hutchinson Cancer Research Center, and Clinical Director of the Gastrointestinal Medical Oncology program at Seattle Cancer Care Alliance, found the efficacy of ...

Pancreatic Cancer
Genomics/Genetics

CodeBreaK 100: Sotorasib Shows Activity in KRAS G12C–Mutated Pancreatic Cancer

Promising activity in metastatic pancreatic cancer was shown by sotorasib, an inhibitor of the KRAS G12C mutation, in the phase I/II CodeBreaK 100 study presented by John H. Strickler, MD, Associate Professor of Medicine at Duke University Medical Center, Durham, North Carolina, during the February ...

Pancreatic Cancer
Genomics/Genetics

Expert Point of View: Mandana Kamgar, MD, MPH

The ASCO Post invited Mandana Kamgar, MD, MPH, Assistant Professor of Medicine at the Medical College of Wisconsin, LaBahn Pancreatic Cancer Program, Milwaukee, to comment on the KRYSTAL-1 trial. “The KRYSTAL-1 study in totality is a multiphase and multiarm ongoing study exploring the role of...

Pancreatic Cancer
Genomics/Genetics

KRYSTAL-1: Adagrasib Controls Disease in Gastrointestinal Malignancies Beyond Colorectal Cancer

A disease control rate of 100% was achieved in gastrointestinal cancers treated with the KRAS G12C inhibitor adagrasib in the phase II KRYSTAL-1 trial, presented at the 2022 ASCO Gastrointestinal Cancers Symposium.1 The population included primarily those with pancreatic cancer; other noncolorectal ...

Genomics/Genetics

I Enrolled in the WISDOM Study and Learned I Am at High Risk for Cancer

I have always been interested in volunteering my services and helping others, so when I got an e-mail asking if I’d like to participate in the WISDOM (Women Informed to Screen Depending on Measures of Risk) study (www.thewisdomstudy.org) I signed on. The study plans to enroll 100,000 diverse women...

Survivorship
Genomics/Genetics

Study Identifies Genetic Variants That May Contribute to Accelerated Aging in Childhood Cancer Survivors

Scientists from St. Jude Children’s Research Hospital have identified variants in two genes that may be associated with accelerated aging in childhood cancer survivors. Their research looked at the difference between the survivors’ biologic age and chronologic age. The study, published by Dong et...

Gynecologic Cancers
Genomics/Genetics

HRR Mutational Status May Be Prognostic of Survival Outcomes for Women With Recurrent Platinum-Sensitive Ovarian Cancer

Results of a biomarker analysis of the NRG Oncology NRG-GY004 trial were presented during the Society for Gynecologic Oncology’s (SGO) Annual Meeting on Women’s Cancer. The analysis, which occurred as part of a preplanned translational endpoint for the study, concluded that homologous recombination ...

Gynecologic Cancers
Genomics/Genetics

Genetic Testing of Samples From Deceased Patients With Tubo-ovarian Cancer to Inform Families of Identification of Pathogenic Variants

As reported in the Journal of Clinical Oncology by Delahunty et al, an Australian pilot study of a genetic testing program (TRACEBACK) for deceased patients with tubo-ovarian cancer was successful in identifying pathogenic variants in samples from the patients, informing family, and engaging family ...

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