Study Identifies MET Amplification as a Driver for Some Non–Small Cell Lung Cancers
A study published by D. Ross Camidge, MD, PhD, and colleagues in the Journal of Thoracic Oncology has helped to define MET amplification as a rare but potentially actionable driver for non–small cell lung cancer (NSCLC). Dr. Camidge said many of the major developments in the treatment of NSCLC have ...
Metastatic Castration-Resistant Prostate Cancer and DNA Repair Gene Alterations
In this video, Drs. Matthew R. Smith, Xin Gao, and Alicia K. Morgans discuss the role of PARP inhibitors in the treatment of metastatic castration-resistant prostate cancer and homologous recombination repair deficiency, focusing on data from the PROfound trial. Dr. Smith presents a case of a 67-year-old man with metastatic castration-resistant prostate cancer who experienced disease progression despite treatment with enzalutamide, and the faculty discuss the use of docetaxel vs olaparib when tumor genomic testing reports pathogenic mutations in BRCA2 or ATM.
Consensus Statement From IASLC on Liquid Biopsy for Advanced NSCLC
As reported in the Journal of Thoracic Oncology by Christian Rolfo, MD, PhD, and colleagues, the International Association for the Study of Lung Cancer (IASLC) has issued a consensus statement on the use of liquid biopsy in advanced non–small cell lung cancer (NSCLC). Select recommendations are...
Prevalence of Homologous Recombination Deficiency in Patients With Pancreatic Cancer
In a systematic review and meta-analysis reported in the Journal of Clinical Oncology, Casolino et al identified the prevalence of homologous recombination deficiency (HRD) genes in patients with pancreatic ductal adenocarcinoma and found that the reported prevalence of HRD was higher with...
Genomic Characteristics of Pediatric Rhabdomyosarcoma Tumors
In an analysis from an international consortium reported in the Journal of Clinical Oncology, Shern et al identified genomic characteristics and associated outcomes in pediatric rhabdomyosarcoma. Among the findings were that MYOD1 and TP53 mutations were associated with poorer outcomes. As stated...
Expert Point of View: Edward B. Garon, MD, MS
Invited discussant of the BOOSTER trial,1 Edward B. Garon, MD, MS, Professor of Medicine and Director of the Thoracic Oncology Program, David Geffen School of Medicine at the University of California Los Angeles, said the study’s research question is appropriate, since osimertinib was established...
Study Finds Bevacizumab Offers No Boost to Second-Line Osimertinib in EGFR T790M–Mutated Lung Cancer
For the second-line treatment of advanced EGFR T790M–mutated non–small cell lung cancer (NSCLC), the performance of osimertinib alone was not found to be different from that of osimertinib plus bevacizumab in the phase II ETOP 10-16 BOOSTER trial, reported at a European Society for Medical...
Expert Point of View: Nicolas Girard, MD, PhD
Invited discussant Nicolas Girard, MD, PhD, of the Curie Institute, Paris, said, “A major challenge in NSCLC is what happens when osimertinib resistance develops.” “A key takeaway point from this study is that the efficacy is driven by resistance mechanism. The overall response rate was 47% in the ...
Amivantamab/Lazertinib Combination May Overcome Osimertinib Resistance in Patients With EGFR-Positive NSCLC
Combination targeting of epidermal growth factor receptor (EGFR) with amivantamab/lazertinib achieved durable responses in more than one-third of chemotherapy-naive patients with EGFR-mutant non–small cell lung cancer (NSCLC) that had progressed on osimertinib, according to a cohort analysis of the ...
Disease Risk Associated With Protein-Truncating and Rare Missense Variants in Breast Cancer Risk Genes
In a study reported in TheNew England Journal of Medicine, Leila Dorling, PhD, of the Centre for Cancer Genetic Epidemiology, Departments of Public Health and Primary Care, University of Cambridge, United Kingdom, and colleagues in the international Breast Cancer Association Consortium (BCAC),...
Mechanisms of Acquired Resistance to KRAS G12C Inhibition in Patients With Cancer
In a study reported in The New England Journal of Medicine, Awad et al identified potential mechanisms of acquired resistance to the KRAS G12C inhibitor adagrasib in patients receiving the agent for treatment of KRAS G12C–mutant cancers. As noted by the investigators, clinical trials of the KRAS...
Study Explores Co-occurring Mutations in HER2 and HER3
Mutations in a gene related to HER2, a gene frequently implicated in breast cancers and a variety of other malignancies, can amplify activity that spurs tumor growth, according to a new study. The findings, published by Hanker et al in Cancer Cell, could explain why many patients with HER2...
Use of Germline Mutation Profiling in Patients With Advanced Cancers
In a study reported in the Journal of Clinical Oncology, Zsofia K. Stadler, MD, and colleagues found that germline mutation testing revealed therapeutically actionable variants in 8% of patients with recurrent or metastatic cancers, with 40% of them receiving directed treatment. As stated by the...
How RAS Mutations in Early-Onset Colorectal Cancer May Impact Patient Survival
Although both incidence and mortality rates in colorectal cancer have been declining among people older than 65 by 3.3% and 3% annually, respectively, among individuals younger than age 50, the incidence rate has risen about 2% annually, and death rates have increased by 1.3% annually.1 Colorectal...
Prevalence of Germline BRCA Mutations in Women With Ovarian Cancer in India
In a prospective cross-sectional study reported in JCO Global Oncology, Gupta et al found that women with ovarian cancer in India had a high prevalence of pathogenic or likely pathogenic BRCA variants. As stated by the investigators: “There are deficient data on prevalence of germline mutations in...
Retrospective Study Explores Variation in Colorectal Cancer Risk in Families With Lynch Syndrome
In a retrospective cohort study reported by Win et al in The Lancet Oncology, researchers in the International Mismatch Repair Consortium found marked variation in the risk of colorectal cancer in families with Lynch syndrome carrying the same pathogenic variant in DNA mismatch repair genes. The...
Effect of Polygenic Risk Score on Estimated Breast Cancer Risk Among Carriers of Pathogenic Variants in Predisposition Genes
In a study reported in the Journal of Clinical Oncology, Gao et al found that use of a polygenic risk score (PRS) modified the estimated risk of breast cancer among both carriers and noncarriers of established pathogenic variants in breast cancer predisposition genes. Study Details The study...
Alkylating Signature in Colorectal Cancer May Be Linked to High Red Meat Intake
The association between the consumption of red and processed meats and the development of colorectal cancer, as well as pancreatic and prostate cancers, has been known since 2015, when the International Agency for Research on Cancer (IARC) classified the consumption of red meat as probably...
Addition of Gemtuzumab Ozogamicin to Conventional Background Chemotherapy in Pediatric Patients With KMT2A-Rearranged AML
As reported in the Journal of Clinical Oncology by Pollard et al, a subgroup of pediatric patients with KMT2A-rearranged acute myeloid leukemia (AML) in the phase III Children’s Oncology Group AAML0531 trial had improved outcomes with the addition of the CD33-targeting agent gemtuzumab ozogamicin...
ASCO Releases Rapid Guideline Recommendation Update for Patients With High-Risk, HER2-Negative, Germline BRCA–Mutated Breast Cancer
A new ASCO guideline update recommends offering 1 year of adjuvant olaparib to patients with high-risk, early-stage, HER2-negative breast cancer and germline BRCA mutations after completion of (neo)adjuvant chemotherapy and local treatment, including radiation. The recommendations update the 2020...
Pralsetinib in Advanced RET Fusion–Positive NSCLC: ARROW Trial
As reported in The Lancet Oncology by Justin F. Gainor, MD, and colleagues, an interim analysis of the phase I/II ARROW trial has shown that the oral RET inhibitor pralsetinib produced high response rates in previously treated and treatment-naive patients with advanced RET fusion–positive non–small ...
Real-World Survival Outcomes With Targeted Therapy for Intracranial Metastatic Disease
In a retrospective cohort study reported in JAMA Oncology, Erickson et al found that real-world use of targeted therapy after diagnosis of intracranial metastatic disease was associated with improved overall survival vs no use of targeted therapy in patients with HER2-positive breast cancer,...
Global Registry Analysis of NRG1 Fusion–Positive Lung Cancer
In an analysis from the global eNRGy1 registry for NRG1 fusion–positive lung cancers reported in the Journal of Clinical Oncology, Alexander Drilon, MD, and colleagues found greater than expected heterogeneity in characteristics of disease. Additionally, patients had poor responses to cytotoxic,...
Cathy Eng, MD, on Colorectal Cancer: FOLFOXIRI, Cetuximab, and Bevacizumab as First-Line Treatment
Cathy Eng, MD, of Vanderbilt-Ingram Cancer Center, discusses two abstracts from a session she co-chaired: the phase II DEEPER trial, which explored the use of FOLFOXIRI plus cetuximab vs FOLFOXIRI plus bevacizumab as first-line treatment in metastatic colorectal cancer with RAS wild-type tumors; and the phase II FIRE-4.5 study, which investigated FOLFOXIRI plus either bevacizumab or cetuximab as first-line treatment of BRAF V600E–mutant advanced disease (Abstracts 3501 and 3502).
Expert Point of View: Christine Lovly, MD, PhD
Invited discussant Christine Lovly, MD, PhD, Associate Professor of Medicine, Ingram Associate Professor of Cancer Research, Vanderbilt University Ingram Cancer Center, Nashville, discussed progress in targeted therapies for NSCLC. “We have a tremendous amount of knowledge about driver mutations in ...
More Widespread Biomarker Testing for NSCLC in Oncology Practices and More Testing in Black Patients: An Urgent Priority
Even though next-generation sequencing is recommended by the National Comprehensive Cancer Network (NCCN) for biomarker testing for patients with non–small cell lung cancer (NSCLC), the uptake among community oncology practices is suboptimal, and the uptake is even lower among Black patients with...
Sotorasib for KRAS G12C–Mutated NSCLC: Overall Survival and Exploratory Subgroup Analyses
Results from the phase II cohort of the CodeBreaK 100 study showed that treatment with the KRAS G12C inhibitor sotorasib achieved a 37.1% objective response rate and a median overall survival of 12.5 months in previously treated patients with KRAS G12C–mutated non–small cell lung cancer (NSCLC)....
Pasi A. Janne, MD, PhD, on NSCLC: Patritumab Deruxtecan to Target HER3
Pasi A. Janne, MD, PhD, of Dana-Farber Cancer Institute, discusses study findings that show patritumab deruxtecan is effective in patients with EGFR-mutated and inhibitor-resistant non–small cell lung cancer. Dr. Janne also explains why targeting HER3, a mutation expressed in most EGFR-altered cancers, is a beneficial treatment approach (Abstract 9007).
Andrew Tutt, PhD, MBChB, on Breast Cancer: Olaparib After Chemotherapy in Germline BRCA1/2–Mutated Tumors
Andrew Tutt, PhD, MBChB, of the Institute of Cancer Research, London, discusses findings from the phase III OlympiA trial, which showed that adjuvant olaparib, a PARP inhibitor, following adjuvant or neoadjuvant chemotherapy, may improve invasive disease–free survival in patients with germline BRCA-mutated and high-risk HER2-negative early breast cancer, which might lead to a new indication in this setting (Abstract LBA1).
OlympiA: Adjuvant Olaparib Extends Disease-Free Survival in BRCA-Mutated Early-Stage HER2-Negative Breast Cancer
One year of adjuvant therapy with the PARP inhibitor olaparib extended disease-free survival in patients with high-risk, early-stage, HER2-negative breast cancer with BRCA1/2 germline mutations, according to a prespecified interim analysis of the phase III OlympiA trial presented by Andrew Tutt, MB ...
Pertuzumab/Trastuzumab Demonstrates Activity in Tissue-Agnostic Trial for Patients With HER2-Positive Tumors
Results from the phase II MyPathway basket trial found that the HER2-targeted therapies pertuzumab and trastuzumab demonstrated durable activity in patients with a wide variety of tumors marked by HER2 amplification or overexpression, although responses were limited in those with KRAS mutations....
Are There Differences in the Prevalence of Germline Pathogenic Variants in Susceptibility Genes in Black vs White Women With Breast Cancer?
In a population-based study reported in JAMA Oncology, Susan M. Domchek, MD, and colleagues found “no clinically meaningful differences” in the prevalence of germline pathogenic variants in 12 established breast cancer susceptibility genes between Black and non-Hispanic White women with breast...
FDA Grants Accelerated Approval to Infigratinib for Metastatic Cholangiocarcinoma With an FGFR2 Fusion or Rearrangement
On May 28, 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the kinase inhibitor infigratinib (Truseltiq) for adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or ...
FDA Approves Sotorasib for KRAS G12C–Mutated NSCLC
On May 28, the U.S. Food and Drug Administration (FDA) approved sotorasib (Lumakras) as the first treatment for adult patients with non–small cell lung cancer (NSCLC) whose tumors have a KRAS G12C genetic mutation and who have received at least one prior systemic therapy. This is the first approved ...
Actionable Mutations Identified in Majority of Genome-Sequenced Resected Cholangiocarcinomas
Tumor genomic profiling of resected cholangiocarcinomas may reveal mutations targetable with agents currently being used for other cancers, according to the results of a study presented at the Society of Surgical Oncology (SSO) 2021 International Conference on Surgical Cancer Care.1 Among patients...
FDA Grants Accelerated Approval to Amivantamab-vmjw for Metastatic EGFR Exon 20 Insertion–Mutated NSCLC
On May 21, the U.S. Food and Drug Administration (FDA) granted accelerated approval to amivantamab-vmjw (Rybrevant), a bispecific antibody directed against epidermal growth factor and MET receptors, for adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) and...
Avapritinib vs Other Tyrosine Kinase Inhibitors for PDGFRA D842V–Mutated Gastrointestinal Stromal Tumors
Data from a study published by Margaret von Mehren, MD, and colleagues in BMC Cancer showed that avapritinib, a platelet-derived growth factor receptor A (PDGFRA) inhibitor, has a “clinically meaningful benefit” for the treatment of gastrointestinal stromal tumors (GIST) with PDGFRA D842V...
Standard Multigene Testing Could Detect More Hereditary Cancer Syndromes in Patients With Colorectal Cancer
Up to 38.6% of people with colon cancer who have a hereditary cancer syndrome—including 6.3% of those with Lynch syndrome—could have their conditions remain undetected with current universal tumor-screening methods, and at least 7.1% of people with colorectal cancer have an identifiable inherited...
Dual BRAF/MEK Inhibition Under Study in BRAF V600E–Mutant Gliomas
The combination of dabrafenib plus trametinib led to encouraging and durable responses in patients with low- and high-grade gliomas harboring BRAF V600E mutations, according to the results of the phase II basket study known as ROAR. Results were presented during the virtual edition of the American...
Mutational Profile of Acral Nevi May Differ From Acral Melanoma
Melanocytic nevi are nonmalignant growths that arise from pigment-producing cells of the skin. They are mostly found in sun-exposed areas; however, they also can be found in sun-protected areas, such as the palms, soles of the feet, and nail beds, where they are known as acral nevi. While the...
ACMG Clinical Practice Resource Provides New Guidance for Management of Individuals With PALB2 Gene Variants
The American College of Medical Genetics and Genomics (ACMG) has released a clinical practice resource from a global team of specialists in cancer genetics that will help inform the clinical management of patients who harbor a PALB2 variant and may be at increased risk of developing breast,...
Maintenance Rucaparib in Patients With Platinum-Sensitive Pancreatic Cancer and Germline or Somatic BRCA1, BRCA2, or PALB2 Variants
In a single-institution phase II study reported in the Journal of Clinical Oncology, Kim A. Reiss, MD, and colleagues found that maintenance treatment with the poly (ADP-ribose) polymerase (PARP) inhibitor rucaparib produced responses and was associated with good progression-free survival in...
Surveillance Protocol and Early Cancer Detection in Patients With Constitutional Mismatch Repair Deficiency Syndrome
As reported in the Journal of Clinical Oncology by Durno et al in the International Replication Repair Deficiency Consortium (IRRDC), use of an IRRDC surveillance protocol was associated with improved overall survival among patients with constitutional mismatch repair deficiency syndrome (CMMRD)....
ASCO and Ontario Health Publish Joint Update on Guideline for Targeted Therapy in NSCLC With Driver Alterations
ASCO and Ontario Health (Cancer Care Ontario) have jointly published an update1 to the 2017 ASCO guideline2 regarding systemic therapy recommendations for stage IV non–small cell lung cancer (NSCLC) with driver alterations. Guideline Co-Chair Nasser H. Hanna, MD, of the Indiana University Simon...
Expert Point of View: Ursula Matulonis, MD, and Konstantin Zakashansky, MD
Perspectives on ARIEL4 were provided for The ASCO Post by the invited discussant Ursula Matulonis, MD, Professor of Medicine, Harvard Medical School, and Chief of Gynecologic Oncology and the Brock Wilson Family Chair at Dana-Farber Cancer Institute, Boston, and by Konstantin Zakashansky, MD,...
Phase III ARIEL4 Confirms Rucaparib’s Benefit in BRCA-Mutated Relapsed Ovarian Cancer
In patients with BRCA-mutated, advanced, relapsed ovarian cancer, treatment with the PARP (poly [ADP-ribose] polymerase) inhibitor rucaparib led to a significant improvement in progression-free survival compared with standard-of-care chemotherapy, according to results of the international phase III ...
Relationship Between Germline BRCA Pathogenic Variants and Diminished Ovarian Reserve
In a study reported in the Journal of Clinical Oncology, Turan et al found the presence of germline BRCA pathogenic variants was associated with diminished ovarian reserve in young women, particularly in those diagnosed with breast cancer and those with BRCA1 variants. Study Details The individual...
Expanding Role of Liquid Biopsies in Cancer Detection and Therapeutics: Now and in the Near Future
“It is possible that within the next several years, perhaps 75% of cancers can be detected by screening,” Bert Vogelstein, MD, PhD, projected at the Society of Surgical Oncology (SSO) 2021 International Conference on Surgical Cancer Care.1 “I anticipate that perhaps 50% of cancers can be detected...
Expert Point of View: Antoni Ribas, MD, PhD
“This study is important because of the large numbers of genetic samples and the significance of the results,” stated Antoni Ribas, MD, PhD, President of the American Association for Cancer Research and Director of Tumor Immunology at UCLA’s Jonsson Comprehensive Cancer Center. “The study included...
Heritability Genes Identified in Childhood Neuroblastoma
Researchers have made progress in unravelling the genetic underpinnings of pediatric neuroblastoma. Two main inherited pathogenic genetic variants have been identified and appear to be associated with worse outcomes: the ALK gene and loss of function in PHOX2B. The research, conducted with the...
