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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...

Leukemia
Genomics/Genetics

Use of Polygenic Cytarabine Response Score to Identify Candidates With Pediatric AML for Chemotherapy Augmentation

In a study reported in the Journal of Clinical Oncology, Elsayed et al developed a risk score based on single nucleotide polymorphisms (SNPs) associated with cytarabine pharmacodynamics or clinical outcomes that identified pediatric patients with acute myeloid leukemia (AML) who could benefit from...

colorectal cancer
immunotherapy
genomics/genetics

Van K. Morris, MD, on Metastatic Colorectal Cancer: Early Trial Results on Encorafenib, Cetuximab, and Nivolumab

Van K. Morris, MD, of The University of Texas MD Anderson Cancer Center, discusses phase I/II data suggesting that encorafenib plus cetuximab and nivolumab is safe and well tolerated for patients with microsatellite-stable BRAF V600E–mutated metastatic colorectal cancer (Abstract 12).

Leukemia
Genomics/Genetics

New Study Examines Role of Genetic Ancestry in Pediatric Leukemia

Scientists at St. Jude Children’s Research Hospital are studying the impact of genetic ancestry on childhood acute lymphoblastic leukemia (ALL). The scientists assembled an international cohort to determine how genetic ancestry affects leukemia biology and outcomes for modern therapy; they found...

Genomics/Genetics

Risk of Multiple Cancers in Male Carriers of BRCA1 and BRCA2 Gene Mutations

People who carry the BRCA1 or BRCA2 gene mutation have an increased risk of pancreatic, stomach, and prostate cancers, as well as the previously well-known risk of breast and ovarian cancers, according to new research calling for increased testing in male carriers to detect the cancers early. The...

lung cancer
genomics/genetics

Julia Rotow, MD, on Patient Selection in Treating Thoracic Cancers: Looking to Driver Mutations and Biomarkers

Julia Rotow, MD, of Dana-Farber Cancer Institute, discusses an education session she conducted on mutations and biomarkers in thoracic cancers, including PD-L1, a continuous variable, with the greatest benefit to treatment being associated with very high levels of PD-L1 tissue polypeptide-specific antigen. Dr. Rotow also discusses STK11 mutations, which may be associated with reduced benefit to immune checkpoint inhibitor therapy, though further study is needed.

pancreatic cancer
genomics/genetics

Tanios S. Bekaii-Saab, MD, on Pancreatic and Other Tumors With KRAS G12C Mutation: Updated Data on Use of Adagrasib

Tanios S. Bekaii-Saab, MD, of Mayo Clinic, discusses new findings from the KRYSTAL-1 study, which suggested adagrasib monotherapy is well tolerated and demonstrates clinical activity in pretreated patients with unresectable or metastatic pancreatic cancer or other gastrointestinal tumors harboring a KRAS G12C mutation. Adagrasib is an inhibitor of the KRAS G12C mutation (Abstract 519).

Thyroid Cancer
Genomics/Genetics

Association of Genetic Alterations With Disease Characteristics and Response to Treatment in Pediatric Differentiated Thyroid Cancer

In a study reported in the Journal of Clinical Oncology, Franco et al found that RET and NTRK fusions were common somatic genetic alterations in pediatric patients with differentiated thyroid cancer and were associated with an increased risk of metastasis and poorer treatment outcome. Study ...

multiple myeloma
genomics/genetics

Anil Aktas-Samur, PhD, on Identifying Low-Risk Smoldering Multiple Myeloma

Anil Aktas-Samur, PhD, of Dana-Farber Cancer Institute, discusses study findings on the genomic characterization of non-progressor smoldering multiple myeloma, results that may provide a molecular definition of the disease as well as its risk-driving features. Combining this low-risk model with current high-risk models may possibly improve clinical trials for patients with this early precursor to myeloma (Abstract 545).  

leukemia
genomics/genetics

Musa Yilmaz, MD, on FLT3-ITD–Mutated AML: Findings on Quizartinib With Decitabine and Venetoclax

Musa Yilmaz, MD, of The University of Texas MD Anderson Cancer Center, discusses study results suggesting that quizartinib with decitabine and venetoclax is active in patients with FLT3-ITD–mutated acute myeloid leukemia and that RAS/MAPK mutations continue to drive primary and secondary resistance (Abstract 370).

lymphoma
genomics/genetics

Joe Schroers-Martin, MD, on Follicular Lymphoma: Precursor Mutations May Be Detectable Years Before Diagnosis

Joe Schroers-Martin, MD, of Stanford University, discusses his latest study findings, which show that follicular lymphoma driver mutations are detectable in blood and saliva years prior to a clinical diagnosis. These data build on previous work and suggest that researchers may be able to stratify people at elevated risk of clinical malignancy (Abstract 709).

Genomics/Genetics
Immunotherapy

Association of HLA-A*03 With Outcomes of Immune Checkpoint Inhibition for Advanced Cancers

In a study reported in The Lancet Oncology, Naranbhai et al found that the presence of HLA-A*03 was associated with poorer outcomes in patients receiving immune checkpoint inhibitors for advanced cancers. As stated by the investigators, “Predictive biomarkers could allow more precise use of immune...

Hepatobiliary Cancer
Genomics/Genetics

European Genome-Wide Association Study of Genetic Variants in Alcohol-Related Hepatocellular Carcinoma

In a case-control genome-wide association study among persons of European ancestry reported in The Lancet Oncology, Trépo et al identified common genetic variants associated with the risk of alcohol-related hepatocellular carcinoma (HCC). Study Details The study involved a discovery cohort of 2,107 ...

Multiple Myeloma
Immunotherapy
Genomics/Genetics

Molecular Analysis Advances Risk Profiling and Assessment of Immunotherapy Response in Smoldering Myeloma

Molecular and genetic research has advanced the categorization of different risk groups in patients with smoldering myeloma. Notable presentations at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition included reports on biomarkers to predict response to immunotherapy in...

Breast Cancer
Genomics/Genetics

Personalized Therapy vs Physician’s Choice of Treatment for Patients With Residual Triple-Negative Breast Cancer After Neoadjuvant Chemotherapy

In a phase II trial reported in the Journal of Clinical Oncology, Schneider et al found that genomically directed therapy did not improve 2-year disease-free survival vs treatment of physician’s choice in patients with residual triple-negative breast cancer following neoadjuvant chemotherapy. Study ...

Lung Cancer
Genomics/Genetics

Expert Point of View: Myung-Ju Ahn, MD, PhD

Myung-Ju Ahn, MD, PhD, Professor in the Department of Hematology and Oncology at Samsung Medical Center, Sungkyunkwan University School of Medicine, South Korea, said the novel regimen of sintilimab, IBI305, and chemotherapy is a promising approach in EGFR-mutated nonsquamous non–small cell lung...

Lung Cancer
Genomics/Genetics

ORIENT-31: Novel Four-Drug Regimen Evaluated in EGFR-Mutated NSCLC

A four-drug combination of the anti–PD-1 antibody sintilimab, the bevacizumab biosimilar IBI305, plus pemetrexed and cisplatin chemotherapy significantly improved progression-free survival compared with chemotherapy alone in patients with advanced nonsquamous non–small cell lung cancer (NSCLC) with ...

leukemia
genomics/genetics

Eunice S. Wang, MD, on FLT3-Mutated AML: Gilteritinib and Azacitidine for Intensive Induction Chemotherapy–Ineligible Patients

Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, discusses phase III results showing that gilteritinib and azacitidine led to significantly higher composite complete response rates in patients with newly diagnosed FLT3-mutant acute myeloid leukemia who are ineligible for intensive induction chemotherapy. Overall survival was similar to that of azacitidine alone (Abstract 700).  

Lymphoma
Genomics/Genetics
Immunotherapy

Effect of TP53 Alterations on Outcomes of CD19-Targeted CAR T-Cell Therapy for Patients With Large B-Cell Lymphoma

In a single-center retrospective study reported in the Journal of Clinical Oncology, Shouval et al found that the presence of TP53 alterations was associated with poorer outcomes in patients treated with CD19-targeted chimeric antigen receptor (CAR) T-cell therapy (CD19–CAR-T) for relapsed or...

Colorectal Cancer
Genomics/Genetics

Sotorasib in Previously Treated Patients With KRAS G12C–Mutant Colorectal Cancer

In a prespecified analysis of the phase II CodeBreaK100 trial reported in The Lancet Oncology, Marwan Fakih, MD, and colleagues found that the KRAS G12C protein inhibitor sotorasib showed modest activity in patients with previously treated KRAS G12C–mutant colorectal cancer. Study Details The...

leukemia
genomics/genetics

Talha Badar, MD, on TP53-Mutated AML and the Impact of Allogeneic Stem Cell Transplantation on Survival

Talha Badar, MD, of the Mayo Clinic, discusses the near-universal poor outcomes for patients with TP53-mutated acute myeloid leukemia and the findings that show allogeneic stem cell transplantation appears to improve the long-term survival in a subset of these patients. Effective therapies may successfully bridge patients to transplant and prolong survival for those who are transplant-ineligible (Abstract 797).

Leukemia
Genomics/Genetics

Ivosidenib/Azacitidine vs Azacitidine Alone in Patients With Newly Diagnosed IDH1-Mutated AML

In the phase III AGILE trial, the combination of ivosidenib and azacitidine was found to be superior in treating newly diagnosed patients with IDH1-mutated acute myeloid leukemia (AML) compared to azacitidine alone in terms of event-free survival, the study’s primary endpoint. The combination also...

breast cancer
genomics/genetics

Patricia A. Ganz, MD, on Early Breast Cancer, Olaparib, Chemotherapy, and Quality of Life

Patricia A. Ganz, MD, of the University of California, Los Angeles, discusses quality-of-life results from the phase III OlympiA study of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high-risk HER2-negative early breast cancer (Abstract GS4-09).

Breast Cancer
Genomics/Genetics

Patients With Hormone Receptor–Positive Breast Cancer and Emergent ESR1 Mutations May Benefit From Early Switch to Fulvestrant/Palbociclib

Among patients with hormone receptor–positive breast cancer treated with an aromatase inhibitor plus palbociclib, those who displayed a rising ESR1 mutation detected in their blood before disease progression doubled their median progression-free survival following a switch to fulvestrant plus...

Colorectal Cancer
Genomics/Genetics

Association of TP53 Gain-of-Function and Non–Gain-of-Function Mutations With Outcomes in Left-Sided vs Right-Sided Metastatic Colorectal Cancer

In a study reported in the Journal of Clinical Oncology, Pan et al found that overall survival was poorer among patients with metastatic right-sided vs left-sided colorectal cancer with TP53 mutations, driven by poorer outcomes in those with non–gain-of-function mutations, and that gain-of-function ...

Breast Cancer
Genomics/Genetics

Molecular Tumor Profiling May Improve Treatment Matching for Patients With Metastatic Breast Cancer

The use of multigene sequencing and SNP array as a therapeutic decision tool improved the outcomes of patients with metastatic breast cancer if the patients carried alterations classified in the I/II tiers of the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT), according to...

Lung Cancer
Genomics/Genetics

Poziotinib in Previously Treated Patients With NSCLC and HER2 Exon 20 Insertion Mutations

In a cohort of the phase II ZENITH20-2 trial reported in the Journal of Clinical Oncology, Le et al found that the tyrosine kinase inhibitor poziotinib produced responses in previously treated patients with non–small cell lung cancer (NSCLC) and HER2 exon 20 insertion mutations. Study Details In...

Hematologic Malignancies
Issues in Oncology
Genomics/Genetics

Association of Donor Clonal Hematopoiesis With Outcomes in Hematopoietic Stem Cell Transplant Recipients

In a study reported in the Journal of Clinical Oncology, Gibson et al identified significant associations of donor clonal hematopoiesis with outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation (HCT). As stated by the investigators, “Clonal hematopoiesis can be...

CNS Cancers
Genomics/Genetics

Dabrafenib Plus Trametinib in BRAF V600E–Mutant High- and Low-Grade Glioma

In an interim analysis of a phase II basket trial (ROAR) reported in The Lancet Oncology, Patrick Y. Wen, MD, and colleagues found that the combination of dabrafenib and trametinib produced responses in adult patients with recurrent or progressive BRAF V600E–mutant high-grade and low-grade glioma. ...

Skin Cancer
Immunotherapy
Genomics/Genetics

Keith T. Flaherty, MD, on Results From the DREAMseq Trial

Invited discussant of the phase III DREAMseq trial, Keith T. Flaherty, MD, said the findings still leave room for nuanced decision-making.1 Dr. Flaherty is Professor of Medicine at Harvard and Director of the Henri and Belinda Termeer Center for Targeted Therapy at the Massachusetts General...

Skin Cancer
Immunotherapy
Genomics/Genetics

DREAMseq Trial: In Advanced Melanoma With BRAF Mutations, Start With Immunotherapy

 In the treatment of patients with advanced melanoma containing BRAF mutations, initial treatment with an immunotherapy combination achieved superior overall survival compared with targeted therapy in the phase III DREAMseq trial, also known as the ECOG-ACRIN EA6134 trial. The results were reported ...

Genomics/Genetics

Cancer Incidence and Patterns in Individuals With Pathogenic/Likely Pathogenic Germline TP53 Variants

In an observational cohort study reported in The Lancet Oncology, de Andrade et al identified cancer incidence and patterns in individuals meeting criteria for Li-Fraumeni syndrome on the basis of presence of pathogenic or likely pathogenic germline TP53 variants. As stated by the investigators,...

Genomics/Genetics

ALK Inhibition for Pediatric Patients With Advanced ALK-Positive Malignancies

In a phase I dose-escalation and dose-expansion study reported in The Lancet Oncology, Fischer et al found that the ALK inhibitor ceritinib produced durable responses in pediatric patients with relapsed or refractory, locally advanced or metastatic ALK-positive malignancies. Study Details In the...

Issues in Oncology
Genomics/Genetics

Development of Phenotypic Spectrum Categorization for Li-Fraumeni Syndrome

In a study reported in JAMA Oncology, Kratz et al analyzed data from the International Agency for Research on Cancer (IARC) TP53 Database to define a phenotypic spectrum categorization for Li-Fraumeni syndrome. As stated by the investigators, “Li-Fraumeni syndrome is a cancer predisposition...

Hepatobiliary Cancer
Genomics/Genetics

Association of KRAS Variants With Outcomes After Curative Resection of Intrahepatic Cholangiocarcinoma

In a Chinese single-institution cohort study reported in JAMA Surgery, Zhou et al found that the presence of somatic G12 KRAS variants was associated with poorer overall and disease-free survival in patients who had undergone curative resection of intrahepatic cholangiocarcinoma. Study Details The ...

Genomics/Genetics
Issues in Oncology

Study Reveals Genomic Differences Between 14 Tumor Types in Younger vs Older Adults

The results of a study published by Lee et al in Cell Reports suggest that several genetic hallmarks may play key roles in identifying precise treatment options for young adult patients with cancer. The investigators, who systematically compared the genomes of 14 different types of cancers that...

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