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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 ...

Prostate Cancer
Genomics/Genetics

PARP Inhibitor Plus Abiraterone Benefits Subgroups of Patients With Metastatic Castration-Resistant Prostate Cancer

The combination of the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib plus abiraterone acetate and prednisone as first-line therapy significantly improved radiographic progression-free survival vs abiraterone and placebo alone in men with metastatic castration-resistant prostate cancer...

Lung Cancer
Genomics/Genetics
Immunotherapy

Front-Line Toripalimab Plus Chemotherapy Improves Survival in Patients With Advanced NSCLC Without Actionable Mutations

Adding the PD-1 inhibitor toripalimab to chemotherapy significantly improved survival compared with chemotherapy alone in patients with advanced non–small cell lung cancer (NSCLC) without EGFR/ALK mutations, according to research presented by Wang et al during the March 2022 session of the ASCO...

kidney cancer
bladder cancer
prostate cancer
genomics/genetics
immunotherapy
covid-19

Sumanta K. Pal, MD, on Advances in Genitourinary Cancer Treatment: Expert Perspective

Sumanta K. Pal, MD, of City of Hope National Medical Center, discusses some key research developments in kidney cancer, including data on nivolumab and ipilimumab with or without CBM588 in metastatic renal cell carcinoma; intestinal microbiome associated with the development of grade 3 or 4 adverse events in patients with metastatic disease who have been treated with nivolumab plus ipilimumab and probiotic support; the link between TERT promoter mutations and clinical outcome with immune checkpoint inhibitor therapy for advanced urothelial cancer; mutations in the androgen receptor gene in patients with prostate cancer receiving novel androgen deprivation treatments; and findings on waning antibody titers in patients who have received COVID-19 vaccinations (Roundup of Abstracts 371, 561, 374, Posters 38 and 48).

Breast Cancer
Genomics/Genetics

Racial Genomic Profiles of Primary and Metastatic Breast Cancer

In a study reported in a research letter in JAMA Network Open, Goel et al identified genomic differences among Black, Asian, and White patients with breast cancer and found that Black patients have fewer targetable actionable variants than White patients. Study Details The study included patients...

Leukemia
Genomics/Genetics

Mutations Associated With Resistance to Noncovalent BTK Inhibitors in Patients With CLL

In a study reported in The New England Journal of Medicine, Wang et al identified mutations that conferred resistance to noncovalent Bruton’s tyrosine kinase (BTK) inhibitors in patients with chronic lymphocytic leukemia (CLL) and found that some also conferred resistance to covalent BTK...

Breast Cancer
Genomics/Genetics

MRI and Mammography Breast Cancer Screening Strategies for Women With ATM, CHEK2, and PALB2 Pathogenic Variants

In an analysis reported in JAMA Oncology, Lowry et al found that a strategy of annual magnetic resonance imaging (MRI) screening starting at age 30 to 35 years—followed by annual MRI and mammography at age 40—could reduce the risk of breast cancer mortality by more than 50% in women with ATM,...

Breast Cancer
Genomics/Genetics

Prediction Model for BRCA Mutation–Carrying Status in Asian Patients With Breast Cancer

In an Asian study reported in the Journal of Clinical Oncology, Ang et al developed a model for predicting carrier status of pathogenic variants in BRCA1 or BRCA2 among Asian women with breast cancer. As stated by the investigators, “With the development of poly (ADP-ribose) polymerase inhibitors...

Solid Tumors
Genomics/Genetics

Adagrasib in Advanced KRAS G12C–Mutant Solid Tumors

In a first-in-human phase I/Ib study (KRYSTAL-1) reported in the Journal of Clinical Oncology, Ou et al identified the phase II dose of the oral small-molecule KRAS G12C inhibitor adagrasib and found that the agent was active in patients with advanced KRAS G12C–mutant solid tumors. Study Details...

Prostate Cancer
Genomics/Genetics

New Data Validate Clinical Utility of Genomic Classifier Test to Help Guide Therapy for Men With Intermediate-Risk Prostate Cancer

New data validating the clinical utility of the Decipher prostate genomic classifier for guiding treatment selection in men with intermediate-risk prostate cancer was presented at the 2022 ASCO Genitourinary Cancers Symposium (Abstract 269). Data from the randomized phase III NRG/RTOG 0126 study,...

Prostate Cancer
Genomics/Genetics

PARP Inhibitor Plus Abiraterone Benefits Subgroups of Patients With Metastatic Castration-Resistant Prostate Cancer

The combination of the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib plus abiraterone acetate and prednisone as first-line therapy significantly improved radiographic progression-free survival vs abiraterone and placebo alone in men with metastatic castration-resistant prostate cancer...

Solid Tumors
Genomics/Genetics

Copanlisib in Patients With PIK3CA-Mutated Tumors

In a phase II trial reported in the Journal of Clinical Oncology, Damodaran et al found that the phosphoinositide 3-kinase (PI3K) inhibitor copanlisib exhibited activity in patients who have tumors with PIK3CA mutations. The study is a subprotocol (Z1F) of the NCI-MATCH ECOG-ACRIN trial (EAY131), a ...

Bladder Cancer
Genomics/Genetics

Study Examines Predictive Biomarker for Bladder Cancer Survival

Long-term survival data from the first prospective, randomized biomarker validation trial in patients with muscle-invasive bladder cancer being treated with cisplatin-based chemotherapy before surgery are being reported at the 2022 ASCO Genitourinary Cancers Symposium by Thomas W. Flaig, MD, and...

Pancreatic Cancer
Genomics/Genetics

KRAS G12C Inhibitor Sotorasib Shows Activity in Certain Patients With Pancreatic Cancer

Sotorasib, an irreversible inhibitor of KRAS G12C, showed activity in patients with metastatic pancreatic cancer and a KRAS G21C mutation enrolled in the phase I/II CodeBreaK100 study. These findings were presented during the February 2022 ASCO Plenary Series session by John H. Strickler, MD,...

Pancreatic Cancer
Genomics/Genetics

Niraparib in Previously Treated Patients With Metastatic Castration-Resistant Prostate Cancer and DNA Repair Gene Defects

In the phase II GALAHAD trial reported in The Lancet Oncology, Matthew R. Smith, MD, and colleagues found that the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib showed activity in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects whose disease had...

Prostate Cancer
Genomics/Genetics

Comprehensive Genetic Risk Score May Predict Risk of Developing Metastatic Prostate Cancer or Death From Prostate Cancer Across Diverse Populations

A new screening tool (called PHS290) that incorporates 290 inherited genetic variants associated with prostate cancer was able to accurately identify people with high vs low lifetime risks of developing metastatic prostate cancer or dying from prostate cancer. These findings of a genetic risk...

Breast Cancer
Genomics/Genetics
Immunotherapy

Expert Point of View: Angela DeMichele, MD, MSCE

Angela DeMichele, MD, MSCE, the Alan and Jill Miller Professor in Breast Cancer Excellence at the Perelman School of Medicine of the University of Pennsylvania in Philadelphia, commented on NIMBUS1 for The ASCO Post. She said obtaining information on tumor mutational burden is simple, as it is part ...

Breast Cancer
Genomics/Genetics
Immunotherapy

Dual Checkpoint Inhibitor Therapy Elicits Responses in Highly Mutated Breast Cancer

Patients with advanced HER2-negative metastatic breast cancer and high tumor mutational burden achieved responses—often durable—from treatment with the immunotherapy doublet of nivolumab and ipilimumab, according to results of the phase II NIMBUS trial reported at the 2021 San Antonio Breast Cancer ...

Breast Cancer
Genomics/Genetics

Association of Breast Cancer Subtypes With Pathogenic Germline Variants in Nine Breast Cancer Susceptibility Genes

In a study reported in JAMA Oncology, researchers from the Breast Cancer Association Consortium found that pathogenic germline variants in nine breast cancer susceptibility genes were associated with different breast cancer subtypes, although most were also associated with triple-negative disease....

Breast Cancer
Genomics/Genetics

Role of CECR2 Gene in Advanced Triple-Negative Breast Cancer

A new study published by Zhang et al in Science Translational Medicine shows inhibition of the CECR2 gene may prevent triple-negative breast cancer from advancing or metastasizing. The discovery is an early step in finding new therapeutics for triple-negative breast cancer, one of the most...

Genomics/Genetics

Study Provides Insights Into the Genomic Basis of Cancer Metastasis

New findings from researchers at Memorial Sloan Kettering Cancer Center published by Nguyen et al in Cell support an emerging framework in cancer science that views metastasis as not primarily driven by genetic mutations, but rather, by epigenetic changes that occur in cancer cells because of their ...

Genomics/Genetics

Study Examines Risk of Cancers—Other Than Female Breast and Ovarian Cancers—Associated With BRCA1 and BRCA2 Pathogenic Variants

In a study reported in the Journal of Clinical Oncology, Li et al found that pathogenic variants in BRCA1 or BRCA2—recognized risk factors for female breast and ovarian cancers—were also associated with increased risks of male breast, pancreatic, stomach, colorectal, gallbladder, and prostate...

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