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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...
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...
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,...
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...
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.
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.
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 from the recent ARROW and LIBRETTO-001 trials.
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 ...
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...
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...
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,...
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...
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...
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...
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...
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...
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 ...
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.
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...
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...
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...
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...
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...
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 ...
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 ...
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),...
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...
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...
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...
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...
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...
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...
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...
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...
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...
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...
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 ...
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,...
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, 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).
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 ...
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...
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, 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, 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).
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 ...
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....
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...
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 ...
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 ...