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For some precancerous cells, traveling from the bone marrow to the skin can trigger genetic transformations that can result in leukemia, according to a novel study published by Griffin et al in Nature. The new findings may have shed light on what researchers have termed the “genetic travelogue” of...
Narjust Florez, MD, of Dana-Farber Cancer Institute, and Ferdinandos Skoulidis, MD, PhD, of The University of Texas MD Anderson Cancer Center, discuss results of a biomarker subgroup analysis, showing that sotorasib demonstrated consistent clinical benefit vs docetaxel in all molecularly defined subgroups of patients with pretreated KRAS G12C–mutated advanced non–small cell lung cancer (NSCLC). Although no predictive biomarkers were confirmed, novel hypothesis-generating signals were observed (Abstract 9008).
The National Cancer Institute (NCI) has launched a new set of large, precision medicine–based clinical trials—known as the ComboMATCH initiative—that will examine the efficacy of novel drug combinations targeting specific tumor mutations in adult and pediatric patients with cancer. The new...
In a study reported in JACC: CardioOncology, Singh et al found that haptoglobin (HP) gene expression was associated with risk of anthracycline-related cardiomyopathy in childhood cancer survivors. Study Details In the study, messenger RNA sequencing was performed on total RNA from the peripheral...
Three clinical trials demonstrated positive results from the targeted therapy erdafitinib for patients with multiple tumor types harboring FGFR alterations. The data were presented at the 2023 ASCO Annual Meeting. Erdafitinib is an oral medication that blocks the activity of FGFR signaling...
Vorasidenib, an oral dual inhibitor of mutant IDH1/2 enzymes, significantly improved progression-free survival in patients with grade 2 gliomas. This treatment delayed disease progression and was well tolerated. These findings from the INDIGO trial represent a significant step forward in the...
Treatment with osimertinib after surgery significantly lowered the risk of death in adults with completely resected EGFR-mutated stage IB, II, or IIIA non–small cell lung cancer (NSCLC), according to the findings of the international ADAURA study. The research was presented at the 2023 ASCO Annual...
Among patients with extensive-stage small cell lung cancer (SCLC) positive for expression of the Schlafen-11 gene (SLFN11), those who received maintenance treatment with the immune checkpoint inhibitor atezolizumab plus the PARP inhibitor talazoparib had significantly longer progression-free...
Researchers have identified 116 genes as key molecular vulnerabilities for multiple myeloma, according to a novel study published by de Matos Simoes et al in Nature Cancer. The findings demonstrated the potential for these genes to act as leads and help researchers discover new therapeutic options...
In a single-institution study reported in JACC: CardioOncology, Stephanie Feldman, MD, of Memorial Sloan Kettering Cancer Center, and colleagues found that somatic KRAS and STK11 alterations were associated with increased risk of arterial thromboembolism in patients with solid tumors,...
Whole-exome sequencing of a large database identified carriers of mutations associated with hereditary cancer syndromes (ie, hereditary breast and ovarian cancers and Lynch syndrome). What was surprising was that among those carriers, about 40% did not satisfy the existing National Comprehensive...
In the Italian phase II VELO trial reported in JAMA Oncology, Napolitano et al found that anti-EGFR treatment rechallenge with the addition of panitumumab to trifluridine/tipiracil improved progression-free survival in the third-line setting for patients with RAS wild-type metastatic colorectal...
Although hypomethylating agents previously appeared to be a promising treatment option for patients with bladder cancer refractory to immunotherapy, researchers were forced to halt a recent phase II clinical trial after patients experienced either no response to treatment or rapid tumor...
In a modeling study reported in The Lancet Oncology, Huntley et al found that the extension of UK cancer screening programs for breast, prostate, and colorectal cancers to a polygenic risk score (PRS)-defined high-risk group of patients with cancer may improve cancer case detection and avoidance of ...
In a study reported in The New England Journal of Medicine, DeBoy et al found that individuals carrying germline heterozygous loss-of-function mutations in the telomere-related gene POT1 had long telomeres and may be at risk for benign and malignant neoplasms as part of a familial clonal...
In an analysis published in the Journal of Clinical Oncology, Grace K. Dy, MD, and colleagues report 2-year outcomes of the CodeBreaK100 phase I/II trial of sotorasib in previously treated patients with KRAS G12C–mutated locally advanced or metastatic non–small cell lung cancer (NSCLC). According...
In a phase II trial reported in The New England Journal of Medicine, van der Sluis et al found that the addition of blinatumomab—a bispecific T-cell engager molecule targeting CD19—to standard chemotherapy appeared to result in marked improvements in outcome among infants with KMT2A-rearranged...
Researchers have found that studying the landscape of DNA and RNA alterations across multiple organs of metastasis may provide a new direction in cancer therapeutics to address treatment failure, according to a new study published by Liu et al in Nature Medicine. The new findings from analyzing...
Researchers may have discovered a new therapeutic target for patients with breast cancer—the TONSL gene—while attempting to understand the mechanisms behind breast cancer cell pathogenesis, according to a novel study published by Khatpe et al in Cancer Research. “Most of the cancer research to date ...
In the phase I/II KRYSTAL-1 trial, the KRAS inhibitor adagrasib demonstrated promising clinical activity in previously treated patients with pancreatic ductal adenocarcinoma, biliary tract cancer, and other solid tumors harboring KRAS G12C mutations, according to research presented at the April...
In three new clinical trials, researchers have found that the novel fibroblast growth factor receptor (FGFR) inhibitor pemigatinib and new poly (ADP ribose) polymerase (PARP)/ataxia telangiectasia and Rad3-related (ATR) inhibitor combinations may be effective at treating patients with multiple...
Researchers have discovered that co-occurring mutations in three tumor-suppressor genes—KEAP1, SMARCA4, and CDKN2A—may be linked with poor clinical outcomes in patients with KRAS G12C–mutant non–small cell lung cancer (NSCLC) who were treated with the KRAS G12C inhibitors adagrasib or sotorasib,...
In a single-institution study reported in JACC: CardioOncology, Feldman et al found that somatic KRAS and STK11 alterations were associated with increased risk of arterial thromboembolism in patients with solid tumors, irrespective of tumor type. Study Details The retrospective cohort study used...
Researchers revealed that 39.2% of patients who consented to whole-exome sequencing and were identified as carriers of predisposition genes for hereditary breast and ovarian cancer or Lynch syndrome did not qualify for genetic screening under current guidelines, according to new findings presented...
Researchers have found that a combination of the PARP inhibitor olaparib and the investigational ATR inhibitor ceralasertib showed clinical benefit in pediatric patients with solid tumors exhibiting DNA replication and/or damage repair deficiencies, according to new findings presented by Gatz et al ...
Although plasma cell-free DNA (cfDNA) tests represent a promising approach for cancer screening, different methodologies vary in performance and many liquid biopsy tests show decreased performance in detecting early-stage or low-shedding DNA tumors. However, the results from a retrospective...
Black individuals are disproportionately affected by colorectal cancer. They have the highest rates of the disease of any racial or ethnic group in the United States, and are about 20% more likely to develop colorectal cancer and about 40% more likely to die of the disease than most other groups. A ...
Hereditary cancer syndromes are caused by a pathogenic variant in cancer susceptibility genes, which overall account for approximately 10% of all cancers. Carriers of pathogenic variants are at an increased risk of developing cancer during their lifetime. Genomic cancer risk assessment makes it...
In an analysis of the German phase II PanaMa trial reported in the Journal of Clinical Oncology, Stahler et al evaluated consensus molecular subtypes as prognostic and predictive biomarkers in patients with RAS wild-type metastatic colorectal cancer receiving fluorouracil and leucovorin with or...
Researchers have developed a novel combination therapy approach to help patients with KMT2A-mutated acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) overcome resistance to bromodomain and extraterminal domain (BET) inhibitors without adding toxicity, according to a novel study...
In a prospective cohort study reported in The Lancet Oncology, Asif et al found that endoscopic surveillance may be an alternative to prophylactic total gastrectomy in patients at risk for hereditary diffuse gastric cancer due to germline CDH1 pathogenic variants. Study Details In the study, 270...
In a Japanese study reported in The New England Journal of Medicine, Usui et al found that Helicobacter pylori infection affected the risk of gastric cancer in patients with predisposing germline pathogenic variants, including variants in homologous recombination genes. As stated by the...
New long-term data from the CHRYSALIS study evaluating amivantamab-vmjw in patients with advanced non–small cell lung cancer (NSCLC) and EGFR exon 20 insertion mutations whose disease progressed on prior platinum-based chemotherapy were presented by Lopez et al at the 2023 European Lung Cancer...
As reported in the Journal of Clinical Oncology by Kim N. Chi, MD, and colleagues, the phase III MAGNITUDE trial showed that the addition of niraparib to abiraterone acetate and prednisone improved radiographic progression–free survival as first-line treatment in patients with metastatic...
In a study reported in a research letter in JAMA Oncology, Konstantinidou et al found that the prevalence of hypercalcemia increased over time in patients with cholangiocarcinoma and was significantly more common in those with IDH1-mutant intrahepatic disease. Study Details The study involved...
Researchers have revealed the potential mechanisms contributing to treatment resistance in patients with melanoma at the end of life, according to a new study published by Spain et al in Cancer Discovery. “These results present the most detailed picture yet of what melanoma looks like at the final...
In a study reported in the Journal of Clinical Oncology, Sarfaty et al identified novel genetic subtypes of urothelial carcinoma exhibiting different responses to immune checkpoint blockade. Study Details In the multicenter study, whole-exome sequencing was performed on tumor specimens from 88...
As reported in the Journal of Clinical Oncology by de Braud et al, findings in the expansion cohort of a phase Ib trial indicate activity with the combination of the BRAF/CRAF kinase inhibitor naporafenib and trametinib in patients with advanced or metastatic NRAS-mutant melanoma. Study Details In ...
Obesity may spur DNA damage in the breast tissue of patients who carry BRCA1 or BRCA2 mutations, possibly contributing to breast cancer development in patients who are already at a higher risk of the disease, according to a new study published by Bhardwaj et al in Science Translational Medicine....
As reported in The Lancet by Adrianus Johannes de Langen, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, and colleagues, the phase III CodeBreaK200 trial has shown a small but significant improvement in progression-free survival with sotorasib vs docetaxel in previously treated advanced...
As reported in The New England Journal of Medicine by Karim Fizazi, MD, PhD, of Gustave Roussy Institute, Paris-Saclay University, and colleagues, the phase III TRITON3 trial has shown significantly improved progression-free survival with rucaparib vs physician-selected single-agent therapy in the...
This is Part 2 of The Evolving Targeted Treatment Landscape for Colorectal Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. John Strickler, Stacey A. Cohen, and Harshabad Singh discuss the management of BRAF V600E–mutated colorectal cancer. The patient is a 40-year-old woman who presents to the ER with severe abdominal pain. CT scan of the chest, abdomen, and pelvis reveals a cecal mass with adjacent nodularity, abdominal lymphadenopathy, and multiple liver lesions consistent with metastatic disease. Colonoscopy demonstrates a nonobstructing mass in the ascending colon; pathology confirms adenocarcinoma, and biopsy of liver lesion confirms adenocarcinoma consistent with colorectal primary. Her performance status is limited due to severe abdominal pain related to her metastatic disease. The patient is started on FOLFOX plus bevacizumab, which results in an improvement in her pain and performance status. Next-generation sequencing reveals APC, SMAD4, and TP53 mutations, as well as a BRAF V600E mutation. The faculty discuss the treatment options for patients with aggressive BRAF V600E mutations, which are associated with poor prognosis and EGFR resistance, in both the first- and second-line setting. They also highlight importance of individualizing treatment based on a patient’s age, performance status, goals of treatment, and comorbidities.
Use of the novel menin inhibitor revumenib has led to remissions in patients with acute myeloid leukemia (AML), and associated findings have suggested the mechanisms through which cancer cells may become resistant to such treatment, according to two studies published by Issa et al and Perner et al, ...
Testing for genetic mutations in urine may help clinicians detect bladder cancer years before the disease shows clinical symptoms, according to new findings presented by Le Calvez-Kelm et al at the 2023 European Association of Urology Annual Congress (Abstract A0268). The researchers identified...
In a Dutch study reported in the Journal of Clinical Oncology, Stroot et al identified the prevalence of high-grade serous carcinoma at risk-reducing salpingo-oophorectomy in asymptomatic BRCA1/2 pathogenic variant carriers. Study Details The study included asymptomatic BRCA1/2 pathogenic variant...
In a study reported in the Journal of Clinical Oncology, Anita Y. Kinney, PhD, RN, and colleagues found that a phone-based tailored risk counseling and navigation intervention resulted in a higher proportion of patients with ovarian or high-risk breast cancers receiving cancer genetic risk...
Discussant of the INTRIGUE abstract, Breelyn A. Wilky, MD, Director of Sarcoma Medical Oncology, Deputy Associate Director for Clinical Research, University of Colorado, Aurora, called the data presented “compelling evidence of the power of ctDNA [circulating tumor DNA] to identify predictive...
Circulating tumor DNA (ctDNA) analysis of KIT exon mutations may help to predict which second-line therapy is best for patients with advanced gastrointestinal stromal tumor (GIST), according to data presented during the ASCO Plenary Series: January 2023 Session.1 Exploratory analysis of the phase...
Researchers have discovered that whole-genome sequencing—rather than the current standard of exome sequencing—may allow physicians to better identify genetic changes that drive cancer development and growth, and create the most effective, personalized treatment plans for patients with classical...
KRAS G12C–mutated colorectal cancer represents 3% to 4% of metastatic colorectal cancers. Like other KRAS-mutated metastatic colorectal cancers, this group of patients represents a patient population with an unmet need, with limited options beyond two lines of therapy. In contrast to other KRAS...