ATR Inhibitor Ceralasertib in ARID1A-Deficient and ARID1A-Intact Solid Tumors
In an ongoing phase II study, Aggarwal et al evaluated the efficacy of the ATR inhibitor ceralasertib alone and in combination with olaparib in patients with ARID1A-deficient and ARID1A-intact solid tumors. They observed antitumor activity with ceralasertib monotherapy in ARID1A-deficient solid...
Expert Point of View: Nadine M. Tung, MD
Formal discussant of the OlympiA trial, Nadine M. Tung, MD, Director of Breast Medical Oncology and the Cancer Genetics and Prevention Program at Beth Israel Deaconess Medical Center and Harvard Medical School, was enthusiastic about the ability of olaparib to improve invasive disease–free survival ...
OlympiA Trial: Adjuvant Olaparib Extends Disease-Free Survival in BRCA-Mutated Early Breast Cancer
Adjuvant therapy with the PARP inhibitor olaparib for 1 year extended disease-free survival in patients with high-risk early-stage HER2-negative breast cancer with BRCA1/2 germline (inherited) mutations, according to a prespecified interim analysis of the phase III OlympiA trial presented at the...
Survey Examines Oncology Clinician Perceptions of Biomarker Testing for Underserved Patients With Lung Cancer
Less than half of community oncologists surveyed indicated that they use biomarker testing to guide patient discussions compared with 73% of academic clinicians, according to a report by Boehmer et al presented at the International Association for the Study of Lung Cancer (IASLC) 2021 World...
Prevalence of Germline BRCA Mutations in Indian Women With Ovarian Cancer
Ovarian cancer is one of the most common gynecologic cancers, with 313,959 new cases and 207,252 deaths reported worldwide in 2020.1 Since there is no effective screening method, ovarian cancer in general is diagnosed in its late stage. The 5-year survival rate in women with ovarian cancer is less...
High Prevalence of Germline BRCA Mutations in Indian Women With Ovarian Cancer
In a prospective cross-sectional study reported in JCO Global Oncology, Sudeep Gupta, MBBS, MD, DM, of Tata Memorial Centre, and colleagues found that Indian women with ovarian cancer not selected for study based on clinical factors had a high prevalence of germline pathogenic or likely pathogenic...
A Scientific Detective Tale With Consequences for the Future of Our Species
With completion of the Human Genome Project, medicine hit a turning point that enabled scientists to approach genetic diseases like cancer with new tools such as disruptive technologies like CRISPR (clustered regularly interspaced short palindromic repeats) gene editing. Progress in this novel...
Genomic Analysis of Lung Cancer in Never-Smokers
A genomic analysis of lung cancer in people with no history of smoking has found that a majority of these tumors arise from the accumulation of mutations caused by natural processes in the body. This study was conducted by an international team led by researchers at the National Cancer Institute...
Cell-Free DNA Analysis to Distinguish Development of Malignant Peripheral Nerve Sheath Tumors From Plexiform Neurofibromas
The inherited condition neurofibromatosis type 1, or NF1, is responsible for the development of benign tumors that grow along the nerves; in some individuals, however, these benign tumors transform into aggressive and malignant peripheral nerve sheath tumors. Determining whether this transformation ...
Effect of Concurrent Focal 22q11.22 Deletions and IKZF1 Alterations on Outcomes in Pediatric Patients With B-Cell ALL
In a study reported in JAMA Oncology, Mangum et al found that focal deletions in chromosome 22q11.22 were associated with poor outcomes in pediatric patients with B-cell acute lymphoblastic leukemia (ALL) with IKZF1 alterations. As stated by the investigators, “Alterations in the IKZF1 gene drive...
ALK Fusion–Positive High-Grade Glioma: Response to Lorlatinib in a Single Pediatric Case
In a letter to the editor published in The New England Journal of Medicine, Bagchi et al describe the course of treatment in a 3-year-old child with an intracranial tumor and his response to therapy with the kinase inhibitor lorlatinib. Key Points Magnetic resonance imaging (MRI) of the head in a...
Liquid Biopsy Is Changing Colon Cancer Management
The measurement of circulating tumor DNA (ctDNA) is changing the way gastrointestinal cancers are managed, according to Bassel F. El-Rayes, MD, Professor and Vice Chair for Clinical Research in the Department of Hematology and Oncology, Emory University, and Associate Cancer Center Director,...
Cancer Predisposition Screening Tool for Predicting Subsequent Malignancies in Childhood Cancer Survivors
In a Canadian study reported in the Journal of Clinical Oncology, Cullinan et al found that the McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) tool provided predictive value for risk of subsequent malignant neoplasms in childhood cancer survivors beyond risk associated with treatment...
ALK-Positive Non–Small Cell Lung Cancer
In this video, Drs. Justin F. Gainor, Ibiayi Dagogo-Jack, and Jyoti D. Patel discuss current treatment options for ALK fusion–positive non–small cell lung cancer (NSCLC). Dr. Gainor presents the case of a 31-year-old patient with minimal tobacco exposure who was diagnosed with metastatic NSCLC. PD-L1 immunohistochemistry revealed a tumor proportion score of 90%, and an EML4-ALK fusion was found on targeted next-generation sequencing. The faculty discuss the importance of testing for oncogenic drivers even in the presence of high PD-L1 expression and review the different generations of ALK inhibitors and their distinguishing features. Finally, they discuss their decision-making processes as it relates to first-line therapy, emphasizing the importance of patient communication, understanding toxicity profiles and resistance, and long-term follow-up.
NTRK Fusion–Positive Non–Small Cell Lung Cancer
In this video, Drs. Justin F. Gainor, Ibiayi Dagogo-Jack, and Jyoti D. Patel discuss the management of NTRK fusion–positive non–small cell lung cancer (NSCLC). Dr. Gainor presents the case of a 44-year-old man with a 5 pack-year history of tobacco exposure who was diagnosed with metastatic NSCLC; molecular testing was initially negative, but subsequent targeted next-generation sequencing revealed an NTRK1 fusion, a key oncogenic driver. The faculty discuss when and where to order additional molecular testing or next-generation sequencing in patients such as this. They review recent clinical data surrounding two agents approved by the FDA for NTRK fusion–driven lung cancer, larotrectinib and entrectinib.
RET Fusion–Positive Non–Small Cell Lung Cancer
In this video, Drs. Justin F. Gainor, Ibiayi Dagogo-Jack, and Jyoti D. Patel discuss the management of RET fusion–positive non–small cell lung cancer (NSCLC). The case presented is a 65-year-old never-smoker patient with metastatic NSCLC who was found to have an EGFR A118V mutation and a KIF5B-RET fusion. The faculty provide background on RET fusions in lung cancer and discuss the different testing modalities used to identify RET alterations. In addition, they discuss how the treatment landscape for these patients has changed in recent years, reviewing data on pralsetinib and selpercatinib from the recent ARROW and LIBRETTO-001 trials.
Study Identifies Possible New Genetic Biomarkers of Pediatric Leukemia
In a study published by Magnum et al in JAMA Oncology, researchers reported on how two separate DNA changes appear to predict aggressive childhood leukemias when they occur in combination. The team evaluated tumor characteristics of more than 1,300 pediatric patients with B-cell acute lymphoblastic ...
Cetuximab Plus Avelumab as Rechallenge Therapy for RAS Wild-Type Metastatic Colorectal Cancer
In an Italian phase II trial reported in JAMA Oncology, Martinelli et al found that cetuximab rechallenge plus avelumab showed activity and was well tolerated in patients with RAS wild-type metastatic colorectal cancer who had responded to first-line chemotherapy plus an anti-EGFR agent and then...
Talazoparib in Patients With Metastatic Castration-Resistant Prostate Cancer and DNA Repair Gene Alterations
In the phase II TALAPRO-1 trial reported in The Lancet Oncology, Johann S. de Bono, PhD, and colleagues found that monotherapy with the poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib produced durable responses in patients with metastatic castration-resistant prostate cancer and DNA...
Simulation Model–Based Clinical Decision Tool for Predicting Benefit of Adjuvant Chemoendocrine vs Endocrine Therapy in HR-Positive, HER2-Negative Breast Cancer
As reported in the Journal of Clinical Oncology, Jayasekera et al have developed a clinical decision tool called BTxChoice that can be used with or without the 21-gene recurrence score to estimate the potential benefit of adjuvant chemoendocrine vs endocrine therapy in women with node-negative,...
Genomic-Adjusted Radiation Dose Model to Predict Radiotherapy Benefit Across Cancer Types
In a study reported in The Lancet Oncology, Scott et al found that application of the genomic-adjusted radiation dose (GARD) model to cohorts of patients with different types of cancer showed a significant association of GARD with benefit of radiotherapy. As stated by the investigators, “We...
Amivantamab for Patients With EGFR Exon 20 Insertion–Mutated NSCLC After Disease Progression on Platinum Therapy
As reported in the Journal of Clinical Oncology by Keunchil Park, MD, PhD, and colleagues, amivantamab-vmjw given at the selected phase II dose in a phase I trial (CHRYSALIS) produced durable responses in patients with EGFR exon 20 insertion–mutated non–small cell lung cancer (NSCLC) whose disease...
Outcomes and Behaviors Among Women Receiving or Declining Their Breast Cancer Polygenic Risk Score
A recent study examined patient-reported outcomes and risk-management behaviors of women choosing to receive or decline their breast cancer polygenic risk scores (PRS). The findings were published by Tatiane Yanes, PhD, and colleagues in Genetics in Medicine. The research aimed to look at how the...
Risk of Breast Cancer in Women Older Than Age 65 With Germline Pathogenic Variants in Predisposition Genes
In a study reported in the Journal of Clinical Oncology, Boddicker et al found that women older than age 65 in the general population who carry germline pathogenic variants in established high-risk breast cancer predisposition genes remain at significant risk of late-onset breast cancer and should...
Can Treatment With Thiopurines Induce Mutations That May Lead to Pediatric Leukemia Relapse?
Chemotherapy has helped make acute lymphoblastic leukemia (ALL) one of the most survivable childhood cancers. Now, a research team has shown how thiopurines may lead to mutations that set patients up for disease relapse. These findings were published by Yang et al in Nature Cancer. The research...
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 ...
