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On August 10, 2022, the U.S. Food and Drug Administration (FDA) granted regular approval to capmatinib (Tabrecta) for adult patients with metastatic non–small cell lung cancer (NSCLC) whose tumors have a mutation leading to mesenchymal-epithelial transition (MET) exon 14 skipping, as detected by an ...
Patients with metastatic non–small cell lung cancer (NSCLC) who received a combined therapy of tremelimumab, durvalumab, and chemotherapy experienced longer overall survival compared with those who received chemotherapy alone, regardless of STK11, KEAP1, or KRAS mutational status. These findings...
Researchers studying the molecular landscape of over 500 patients with relapsed or refractory multiple myeloma discovered a prevalence of activated key oncogenic pathways in these patients—much more than previously thought. Upward of 45% to 65% of NF-κB and RAS/MAPK pathways each had alterations....
1,2-Dichloropropane (1,2-DCP) is a synthetic organic solvent used in the printing industry. It was linked to cholangiocarcinoma in 2013, when printing company employees in Osaka, Japan, exposed to 1,2-DCP were diagnosed with the cancer. Thereafter, the International Agency for Research on Cancer...
Researchers at Massachusetts General Hospital (MGH) who previously developed a blood test for mutations in a gene linked to gliomas have now applied their technology to detect additional mutations—in this case, in the gene that codes for the epidermal growth factor receptor (EGFR). The advance,...
Telling children about their mother’s risk of hereditary breast and/or ovarian cancer does not adversely influence the offspring’s lifestyle or quality of life in the long term, according to a new study published by McDonnell et al in the journal Pediatrics. The study looked at the mutation status...
The effective treatment of patients with brain metastases is an unmet need because, until fairly recently, patients with brain metastases were excluded from clinical trials of systemic therapies. However, the emergence of molecular targeted therapies has allowed a new treatment approach in patients ...
The all-oral combination of dabrafenib plus trametinib—two targeted therapies—significantly improved the overall response rate vs standard-of-care chemotherapy with carboplatin plus vincristine in pediatric patients with BRAF V600 mutation–positive low-grade gliomas. The clinical benefit rate...
In a Dutch study reported in the Journal of Clinical Oncology, Klatte et al provided findings from a 20-year follow-up of a pancreatic cancer surveillance program including carriers of germline CDKN2A pathogenic variants. Study Details The study included 347 carriers in the Netherlands who...
On June 23, the U.S. Food and Drug Administration (FDA) granted accelerated approval for dabrafenib (Tafinlar) plus trametinib (Mekinist) for the treatment of adult and pediatric patients aged 6 years and older with unresectable or metastatic solid tumors with a BRAF V600E mutation whose disease...
Investigators at the American Cancer Society presented results of several studies during poster sessions at the 2022 ASCO Annual Meeting. Summaries of a few of these studies are provided here. COVID-19 and Cancer Mortality According to a new study led by researchers at the American Cancer Society,...
In patients with locally advanced or metastatic pancreatic cancer and KRAS wild-type tumors, novel treatment with the monoclonal antibody nimotuzumab, which targets the epidermal growth factor receptor (EGFR), plus gemcitabine significantly improved overall survival and other outcomes over...
In an analysis from an NRG Oncology/Gynecologic Oncology Group phase II study (GOG-86P) reported in the Journal of Clinical Oncology, Thiel et al looked at outcomes in patients with advanced endometrial cancer treated with bevacizumab added to front-line chemotherapy. The investigators found that...
Researchers have, for the first time, identified genes that may predict response to a therapy for a blood cancer that can have serious side effects for some patients. The therapy, selinexor, is part of the treatment armamentarium for multiple myeloma, but the ability to target its use to patients...
In a study reported in JAMA Network Open, Timothy A. Yap, MBBS, PhD, FRCP, and colleagues found that a substantial proportion of patients with cancer types that lacked hereditary testing guidelines harbored germline pathogenic/likely pathogenic variants. Study Details The study included data from...
Gilberto de Lima Lopes, Jr, MD, MBA, of the Sylvester Comprehensive Cancer Center at the University of Miami, and Matthew Krebs, PhD, of The University of Manchester and The Christie NHS Foundation Trust, discuss results from the CHRYSALIS study. The trial showed that the bispecific antibody amivantamab-vmjw demonstrated antitumor activity, even after prior treatment, in patients with non–small cell lung cancer that exhibits the MET exon 14 skipping mutation (Abstract 9008).
Michael J. Overman, MD, of The University of Texas MD Anderson Cancer Center, and Smitha Krishnamurthi, MD, of the Cleveland Clinic, review three abstracts, all of which enrolled patients with newly diagnosed RAS and BRAF wild-type metastatic colorectal cancer with left-sided primary tumors. The discussion centers on what the study results indicate about the use of an EGFR therapy and weighing the risk to quality of life from rash, in particular (Abstracts LBA3503, LBA3504, LBA3505).
In a study reported in The New England Journal of Medicine, Liu et al found that hypomethylating therapy was associated with upregulation of the oncogene SALL4 in a high proportion of patients with myelodysplastic syndrome. They also identified the gene region that is demethylated and responsible...
FLT3-ITD–mutated acute myeloid leukemia (AML) is an aggressive disease usually resistant to available treatment options, resulting in high front-line response rates but short response durations and low survival rates. Quizartinib—a potent selective FLT3 inhibitor—can work synergistically with...
In a study reported in a research letter in JAMA Oncology, Nimgaonkar et al found that less than half of patients with urothelial cancer who had received first-line platinum-based therapy underwent testing for FGFR alterations and that less than half of patients with susceptible alterations...
Mutations in SF3B1 and U2AF1 can drive overexpression of activated IRAK4—which regulates inflammation and promotes cancer cell growth and survival—and are associated with a poor prognosis for patients with high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Emavusertib is a...
In a study presented at the 2022 ASCO Annual Meeting (Abstract 10502) and simultaneously published in JCO Precision Oncology, Veda N. Giri, MD, and colleagues found that Black men with prostate cancer exhibited a lower frequency and narrower spectrum of germline pathogenic or likely pathogenic...
On June 9, Foundation Medicine, Inc., announced that it has received approval from the U.S. Food and Drug Administration (FDA) for FoundationOne CDx to be used as a companion diagnostic for the two indications of the tyrosine kinase inhibitor entrectinib (Rozlytrek). As a companion diagnostic,...
Neal D. Shore, MD, of the Carolina Urologic Research Center, discusses his study findings, showing that germline genetic testing influenced care for patients with prostate cancer. Men whose genetic test was positive for a pathogenic germline variant received more recommendations for changes to follow-up and treatment, and for testing and counseling of relatives, than did patients with negative or uncertain test results (Abstract 10500).
Nearly 1 million people in the United States are affected by Lynch syndrome, a hereditary cancer condition with markedly elevated risk of gastrointestinal, endometrial, and other cancers. Most of them, however, are unaware of it, or find out only after they have developed cancer. A screening...
Women younger than age 40 with advanced breast cancer often experience more aggressive disease and worse prognoses than their older counterparts. Knowing which types of genetic mutations these patients tend to have may inform treatment strategies and improve outcomes. In a recent study, researchers ...
Although women of African descent experience a higher incidence and mortality from triple-negative breast cancer than women of other races or ethnicities, research findings presented by Hall et al at the 2022 ASCO Annual Meeting showed that the magnitude of gene-specific risks of triple-negative...
A new study led by researchers at the American Cancer Society showed physician, practice, and patient characteristics were associated with oncologists’ ratings of the importance of patient health insurance and out-of-pocket costs for genomic testing in treatment decisions. The findings are being...
New findings from researchers at Memorial Sloan Kettering Cancer Center published by Shukla et al in Nature Communications reported the results of using a comprehensive sequencing approach on 114 pediatric, adolescent, and young adult patients with solid tumors. The researchers found that their...
Matthew L. Meyerson, MD, PhD, of the Dana-Farber Cancer Institute, discusses study findings that suggest the variation in frequency of EGFR and KRAS mutations in lung cancer may be associated with genetic ancestry in patients from Latin America. The results indicate it may be possible to identify germline alleles underpinning this link. Finding a germline locus or loci may impact the development of lung cancers with these mutations and may improve lung cancer prevention and screening for populations of Latin American origin, as well as others.
The first bladder cancer drug targeting a cancer-driving gene mutation has been used relatively little despite its clear efficacy in a clinical trial, suggests a report published as a research letter by Nimgaonkar et al in JAMA Oncology. Researchers analyzed a large, nationwide database of cancer...
The first-in-human, first-in-class trial of the next-generation PARP (poly [ADP-ribose] polymerase) 1–selective inhibitor AZD5305 suggests this drug may be a welcome advance over its U.S. Food and Drug Administration (FDA)-approved predecessors in the treatment of solid tumors with alterations in...
Nickolas Papadopoulos, PhD, of the Sidney Kimmel Comprehensive Cancer Center, discusses early detection as the key to reducing cancer mortality and the lack of tests for many malignancies. Liquid biopsies have the potential to screen for various tumor types, albeit with varying levels of sensitivity. Dr. Papadopoulos discusses his research on such blood tests, following patients prospectively to find the best combination of genetic and epigenetic biomarkers to increase sensitivity (Abstract PL02).
In a single-institution case series reported in a research letter in JAMA Oncology, Terrero et al found that the combination of ipilimumab and nivolumab was active in patients with chemotherapy-refractory metastatic pancreatic or biliary cancer with homologous recombination deficiency (HRD)...
Christine A. Iacobuzio-Donahue, MD, PhD, of Memorial Sloan Kettering Cancer Center, discusses her research on the evolutionary features of advanced stage pancreatic cancers and the insights that may be used to help improve patient outcomes (Abstract PL05).
The human epidermal growth factor (HER) family of receptors are a well-established therapeutic target. Indeed, seminal studies conducted nearly 2 decades ago identified a key association between activating mutations in the kinase domain of the epidermal growth factor receptor (EGFR, also known as...
In a phase II trial (DESTINY-Lung01) reported in The New England Journal of Medicine, Bob T. Li, MD, PhD, MPH, of the Thoracic Oncology and Early Drug Development Service, Memorial Sloan Kettering Cancer Center, New York, and colleagues found that fam-trastuzumab deruxtecan-nxki (T-DXd) showed...
In a study reported in JAMA Oncology, Zeng et al found that germline pathogenic variants in 23 hereditary cancer genes were associated with an increased risk of cancers not previously associated with the variants, as well as an increased risk of multiple non-neoplastic diseases. Study Details The...
Charles L. Sawyers, MD, of Memorial Sloan Kettering Cancer Center, discusses the battle against treatment resistance and how to overcome it, as well as the power of observational clinical data in precision oncology, derived largely from his experience with Project GENIE, and the role of genetic ancestry (Abstract PL02).
Using whole-genome sequencing to contrast genomic alterations in patients with stable Barrett’s esophagus compared to patients whose Barrett’s progressed to esophageal adenocarcinoma, Paulson et al reported that DNA changes presaging esophageal cancer can be spotted years before cancer develops....
Priscilla K. Brastianos, MD, of Harvard Medical School and Massachusetts General Hospital, talks about her efforts to better understand how brain metastases evolve genomically and to test such agents as abemaciclib, paxalisib, and entrectinib, which may stop their growth. Palbociclib, a CDK inhibitor, has already shown potential benefit. A national cooperative group trial is underway in multiple centers to identify novel treatments for patients with brain metastases, who typically have a poor prognosis (Abstract SY38).
Timothy A. Yap, MBBS, PhD, of The University of Texas MD Anderson Cancer Center, discusses results from the PETRA study, a first-in-class, first-in-human trial of the next-generation PARP1-selective inhibitor AZD5305 in patients with BRCA1/2, PALB2, or RAD51C/D mutations in advanced or metastatic ovarian cancer, HER2-negative breast cancer, pancreatic, or prostate cancer. Target engagement was demonstrated across all dose levels, and antitumor activity was observed in selected tumor and molecular subtypes.
In a Japanese case-control study reported in JAMA Oncology, Momozawa et al found that germline BRCA1/2 pathogenic variants were associated with an increased risk of biliary tract, esophageal, and gastric cancers, in addition to an increased risk of cancers that have well-established associations...
This is Part 3 of Updates in Prostate Cancer, a four-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Celestia (Tia) Higano, Julie Graff, and Neal Shore discuss the first-line therapy for BRCA2-mutated metastatic castration-resistant prostate cancer. The patient is a 69-year-old man with new castration-resistant prostate cancer who was previously treated with androgen-deprivation therapy plus docetaxel for metastatic hormone-sensitive prostate cancer and has a known BRCA2 mutation. The faculty discuss their choices for first-line therapy for this patient, reviewing the current NCCN recommendations, the role of PARP inhibitors, and recent data from the PROpel and MAGNITUDE trials.
In a Dutch study reported in the Journal of Clinical Oncology, Heesterbeek et al found that results of noninvasive prenatal testing for fetal aneuploidy screening using cell-free DNA derived from maternal plasma raised suspicion of maternal malignancy in a very small proportion of pregnant women....
Cheryl L. Willman, MD, of the Mayo Clinic Comprehensive Cancer Center, discusses the profound cancer health disparities among Native Americans, exacerbated by low rates of screening and limited access to care. Dr. Willman is heading an effort to promote community engagement in comprehensive genomic sequencing with the hope that researchers will discover novel mutations and genome-wide mutational signatures that can ultimately be translated to improved screening and therapy in this population (Abstract PL03).
Jia Luo, MD, of Dana-Farber Cancer Institute, discusses the emerging class of cancer therapies for allele-specific KRAS inhibitors and the importance of their distinct clinical, genomic, and immunologic features. Because KRAS G12D–mutated non–small cell lung cancer is associated with worse responses to immunotherapy, Dr. Luo believes drug development will need to take these differences into account (Abstract 4117).
John Mascarenhas, MD, Director of the Adult Leukemia Program at The Tisch Cancer Institute at Mount Sinai, New York, commented on the implications of the FIGHT-203 trial, which evaluated pemigatinib in myeloid or lymphoid neoplasms. Pemigatinib is an oral small-molecule receptor tyrosine kinase...
In patients with myeloid or lymphoid neoplasms with FGFR1 rearrangements, pemigatinib produced high and durable response rates, despite patients’ extensive use of prior treatments or hematopoietic stem cell transplantation (HSCT), according to the early results of the multicenter phase II FIGHT-203 ...
In a phase II trial (arm E of the NCI-COG Pediatric MATCH trial) reported in the Journal of Clinical Oncology, Eckstein et al found that the MEK inhibitor selumetinib showed little activity in pediatric and young adult patients with tumors harboring activating MAPK pathway mutations or fusions. As...