Advertisement

Advertisement

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...

Lung Cancer
Genomics/Genetics

Adjuvant Gefitinib vs Cisplatin/Vinorelbine for Completely Resected EGFR-Mutant Stage II to IIIA NSCLC

In the Japanese phase III IMPACT trial reported in the Journal of Clinical Oncology, Tada et al found that adjuvant gefitinib did not improve disease-free survival vs cisplatin/vinorelbine in patients with completely resected stage II to IIIA EGFR-mutant non–small cell lung cancer (NSCLC). In the...

Breast Cancer
Genomics/Genetics

Germline Pathogenic Variants in Cancer Predisposition Genes and Risk for Invasive Lobular Carcinoma of the Breast

In a study reported in the Journal of Clinical Oncology, Yadav et al found that germline pathogenic variants in the cancer predisposition genes ATM, BRCA2, CDH1, CHEK2, and PALB2 were associated with an increased risk of invasive lobular carcinoma of the breast, with no association with BRCA1...

Lymphoma
Head and Neck Cancer
Solid Tumors
Genomics/Genetics
Gynecologic Cancers
Skin Cancer
Immunotherapy

FDA Pipeline: Novel Treatments in Lymphoma, Nasopharyngeal Cancer, Solid Tumors, and More

Recently, the U.S. Food and Drug Administration (FDA) granted Priority Review to agents for several kinds of lymphoma, as well as nasopharyngeal cancer; a Breakthrough Therapy designation for a treatment for patients with NTRK-positive advanced solid tumors; and Fast Track designation for...

Gynecologic Cancers
Genomics/Genetics

Five-Year Follow-up of Olaparib Maintenance for Newly Diagnosed Patients With Advanced BRCA-Mutant Ovarian Cancer

As reported in The Lancet Oncology by Susana Banerjee, MBBS, PhD, and colleagues, 5-year follow-up of the pivotal phase III SOLO-1/GOG 3004 trial has shown a median progression-free survival of 56 months with maintenance olaparib following response to platinum-based chemotherapy in newly diagnosed...

Leukemia
Genomics/Genetics

FDA Approves Asciminib for Philadelphia Chromosome–Positive CML

On October 29, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the kinase inhibitor asciminib (Scemblix) for patients with Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) in chronic phase who have been previously treated with two or more tyrosine...

Breast Cancer
Gastrointestinal Cancer
Genomics/Genetics

Rates of Occult Gastric Carcinoma in Patients With Hereditary Lobular Breast Cancer Due to CDH1 Genetic Variants

In a single-institution prospective cohort study reported in JAMA Surgery, Gamble et al found that patients with hereditary lobular breast cancer due to CDH1 variants also had a high prevalence of occult signet ring cell gastric carcinoma. Study Details The study involved 283 patients from 151...

Prostate Cancer
Genomics/Genetics

First-Round Results of Prostate Cancer Screening for Men With Pathogenic Variants in Mismatch Repair Genes

As reported in The Lancet Oncology by Bancroft et al, the first round of prostate cancer screening in the IMPACT study of men with pathogenic variants in mismatch repair genes showed an increased risk of prostate cancer in carriers of MSH2 and MSH6 variants compared with noncarrier controls. As...

Breast Cancer
Genomics/Genetics
Issues in Oncology

Survey of U.S. Oncologists on Genetic Counseling and Testing for Black Women With Breast Cancer

As reported in the Journal of Clinical Oncology by Ademuyiwa et al, a survey of U.S. breast oncologists showed that physicians believe that Black women with breast cancer face more barriers to genetic counseling and testing compared to White women with breast cancer. Study Details The study...

Leukemia
Genomics/Genetics

Addition of Enasidenib to Azacitidine in Newly Diagnosed IDH2-Mutant Acute Myeloid Leukemia

As reported in The Lancet Oncology by Courtney D. DiNardo, MD, and colleagues, an interim analysis of the phase II portion of a phase Ib/II trial (AG221-AML-005) showed that the addition of the oral mutant IDH2 protein inhibitor enasidenib to azacitidine significantly improved overall response rate ...

cns cancers
genomics/genetics

Diana D. Shi, MD, on IDH-Mutant Gliomas: De Novo Pyrmidine Synthesis Inhibitor Under Study

Diana D. Shi, MD, of Dana-Farber Cancer Institute and Brigham and Women’s Cancer Center, discusses studies being planned and already underway to test BAY 2402234, a de novo pyrimidine synthesis inhibitor that possibly could be used clinically to target IDH-mutant gliomas and may act as a tumor-selective radiosensitizer (Abstract 167).

Lung Cancer
Genomics/Genetics

Mobocertinib for Previously Treated Advanced NSCLC With EGFR Exon 20 Insertion Mutations

On September 15, 2021, the kinase inhibitor mobocertinib was granted accelerated approval by the U.S. Food and Drug Administration (FDA) for adults with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, as detected by an FDA-approved test,...

Skin Cancer
Genomics/Genetics
Immunotherapy

Expert Point of View: Omid Hamid, MD

Commenting on the SECOMBIT trial was Omid Hamid, MD, Chief of Translational Research and Immunotherapy at The Angeles Clinic & Research Institute, a Cedars-Sinai Affiliate, and Co-Director, Cutaneous Malignancy Program, Cedars-Sinai Cancer. Dr. Hamid said SECOMBIT addresses an important...

Skin Cancer
Genomics/Genetics
Immunotherapy

SECOMBIT Trial Evaluates Optimal Treatment Sequencing in BRAF-Mutated Melanoma

Patients with untreated, metastatic BRAF-mutated melanoma may benefit from receiving immunotherapy first, moving to targeted therapy in the second line, data from the updated overall survival analysis of the randomized, phase II SECOMBIT trial suggest.1 The study aimed to define the optimal...

Gynecologic Cancers
Genomics/Genetics

Relationship Between Preexisting TP53 CHIP Variants and Risk of Secondary Myeloid Neoplasms in High-Grade Ovarian Cancer

In a study reported in JAMA Oncology, Kwan et al found that preexisting TP53 clonal hematopoiesis of indeterminate potential (CHIP) variants were associated with increased risk of secondary myeloid neoplasms in patients receiving poly (ADP-ribose) polymerase (PARP) inhibitor therapy with rucaparib...

Lung Cancer
Genomics/Genetics

Mobocertinib for Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive Metastatic NSCLC

In a phase I/II trial reported in JAMA Oncology, Caicun Zhou, PhD, MD, and colleagues found that mobocertinib, a first-in-class oral kinase inhibitor, produced durable responses in platinum-pretreated patients with EGFR exon 20 insertion–positive metastatic non–small cell lung cancer (NSCLC).  The...

Lung Cancer
Genomics/Genetics

Second-Line Sotorasib Plus Afatinib for KRAS-Mutant NSCLC

The combination of the KRAS inhibitor sotorasib with afatinib, a pan-ErbB tyrosine kinase inhibitor, was feasible in treating patients with non–small cell lung cancer (NSCLC) and mutated KRAS whose disease had progressed on prior therapies, including KRAS inhibitors alone, according to interim...

Lung Cancer
Genomics/Genetics

Genomic Profiling of Lung Adenocarcinoma in Never-Smokers vs Smokers

In a study reported in the Journal of Clinical Oncology, Devarakonda et al found that never-smokers with lung adenocarcinoma had a high frequency of RTK/RAS/RAF pathway driver alterations—similar to smokers with lung adenocarcinoma—but also harbored a significantly higher total frequency of...

Genomics/Genetics

Characteristics of Genomically Targeted Single-Patient Use Requests for Pediatric Cancers

In a study reported in the Journal of Clinical Oncology, Sabnis et al analyzed characteristics of genomically targeted single-patient use requests for investigational agents for the treatment of pediatric cancers. These requests were made from pediatric cancer programs over a 5-year period. As...

Advertisement

Advertisement

Advertisement