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The use of multigene sequencing and SNP array as a therapeutic decision tool improved the outcomes of patients with metastatic breast cancer if the patients carried alterations classified in the I/II tiers of the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT), according to...
In a cohort of the phase II ZENITH20-2 trial reported in the Journal of Clinical Oncology, Le et al found that the tyrosine kinase inhibitor poziotinib produced responses in previously treated patients with non–small cell lung cancer (NSCLC) and HER2 exon 20 insertion mutations. Study Details In...
In a study reported in the Journal of Clinical Oncology, Gibson et al identified significant associations of donor clonal hematopoiesis with outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation (HCT). As stated by the investigators, “Clonal hematopoiesis can be...
In an interim analysis of a phase II basket trial (ROAR) reported in The Lancet Oncology, Patrick Y. Wen, MD, and colleagues found that the combination of dabrafenib and trametinib produced responses in adult patients with recurrent or progressive BRAF V600E–mutant high-grade and low-grade glioma. ...
Invited discussant of the phase III DREAMseq trial, Keith T. Flaherty, MD, said the findings still leave room for nuanced decision-making.1 Dr. Flaherty is Professor of Medicine at Harvard and Director of the Henri and Belinda Termeer Center for Targeted Therapy at the Massachusetts General...
In the treatment of patients with advanced melanoma containing BRAF mutations, initial treatment with an immunotherapy combination achieved superior overall survival compared with targeted therapy in the phase III DREAMseq trial, also known as the ECOG-ACRIN EA6134 trial. The results were reported ...
In an observational cohort study reported in The Lancet Oncology, de Andrade et al identified cancer incidence and patterns in individuals meeting criteria for Li-Fraumeni syndrome on the basis of presence of pathogenic or likely pathogenic germline TP53 variants. As stated by the investigators,...
In a phase I dose-escalation and dose-expansion study reported in The Lancet Oncology, Fischer et al found that the ALK inhibitor ceritinib produced durable responses in pediatric patients with relapsed or refractory, locally advanced or metastatic ALK-positive malignancies. Study Details In the...
In a study reported in JAMA Oncology, Kratz et al analyzed data from the International Agency for Research on Cancer (IARC) TP53 Database to define a phenotypic spectrum categorization for Li-Fraumeni syndrome. As stated by the investigators, “Li-Fraumeni syndrome is a cancer predisposition...
In a Chinese single-institution cohort study reported in JAMA Surgery, Zhou et al found that the presence of somatic G12 KRAS variants was associated with poorer overall and disease-free survival in patients who had undergone curative resection of intrahepatic cholangiocarcinoma. Study Details The ...
The results of a study published by Lee et al in Cell Reports suggest that several genetic hallmarks may play key roles in identifying precise treatment options for young adult patients with cancer. The investigators, who systematically compared the genomes of 14 different types of cancers that...
In the Japanese phase III IMPACT trial reported in the Journal of Clinical Oncology, Tada et al found that adjuvant gefitinib did not improve disease-free survival vs cisplatin/vinorelbine in patients with completely resected stage II to IIIA EGFR-mutant non–small cell lung cancer (NSCLC). In the...
In a study reported in the Journal of Clinical Oncology, Yadav et al found that germline pathogenic variants in the cancer predisposition genes ATM, BRCA2, CDH1, CHEK2, and PALB2 were associated with an increased risk of invasive lobular carcinoma of the breast, with no association with BRCA1...
Recently, the U.S. Food and Drug Administration (FDA) granted Priority Review to agents for several kinds of lymphoma, as well as nasopharyngeal cancer; a Breakthrough Therapy designation for a treatment for patients with NTRK-positive advanced solid tumors; and Fast Track designation for...
As reported in The Lancet Oncology by Susana Banerjee, MBBS, PhD, and colleagues, 5-year follow-up of the pivotal phase III SOLO-1/GOG 3004 trial has shown a median progression-free survival of 56 months with maintenance olaparib following response to platinum-based chemotherapy in newly diagnosed...
On October 29, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the kinase inhibitor asciminib (Scemblix) for patients with Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) in chronic phase who have been previously treated with two or more tyrosine...
In a single-institution prospective cohort study reported in JAMA Surgery, Gamble et al found that patients with hereditary lobular breast cancer due to CDH1 variants also had a high prevalence of occult signet ring cell gastric carcinoma. Study Details The study involved 283 patients from 151...
As reported in The Lancet Oncology by Bancroft et al, the first round of prostate cancer screening in the IMPACT study of men with pathogenic variants in mismatch repair genes showed an increased risk of prostate cancer in carriers of MSH2 and MSH6 variants compared with noncarrier controls. As...
As reported in the Journal of Clinical Oncology by Ademuyiwa et al, a survey of U.S. breast oncologists showed that physicians believe that Black women with breast cancer face more barriers to genetic counseling and testing compared to White women with breast cancer. Study Details The study...
As reported in The Lancet Oncology by Courtney D. DiNardo, MD, and colleagues, an interim analysis of the phase II portion of a phase Ib/II trial (AG221-AML-005) showed that the addition of the oral mutant IDH2 protein inhibitor enasidenib to azacitidine significantly improved overall response rate ...
Diana D. Shi, MD, of Dana-Farber Cancer Institute and Brigham and Women’s Cancer Center, discusses studies being planned and already underway to test BAY 2402234, a de novo pyrimidine synthesis inhibitor that possibly could be used clinically to target IDH-mutant gliomas and may act as a tumor-selective radiosensitizer (Abstract 167).
On September 15, 2021, the kinase inhibitor mobocertinib was granted accelerated approval by the U.S. Food and Drug Administration (FDA) for adults with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, as detected by an FDA-approved test,...
Commenting on the SECOMBIT trial was Omid Hamid, MD, Chief of Translational Research and Immunotherapy at The Angeles Clinic & Research Institute, a Cedars-Sinai Affiliate, and Co-Director, Cutaneous Malignancy Program, Cedars-Sinai Cancer. Dr. Hamid said SECOMBIT addresses an important...
Patients with untreated, metastatic BRAF-mutated melanoma may benefit from receiving immunotherapy first, moving to targeted therapy in the second line, data from the updated overall survival analysis of the randomized, phase II SECOMBIT trial suggest.1 The study aimed to define the optimal...
In a study reported in JAMA Oncology, Kwan et al found that preexisting TP53 clonal hematopoiesis of indeterminate potential (CHIP) variants were associated with increased risk of secondary myeloid neoplasms in patients receiving poly (ADP-ribose) polymerase (PARP) inhibitor therapy with rucaparib...
In a phase I/II trial reported in JAMA Oncology, Caicun Zhou, PhD, MD, and colleagues found that mobocertinib, a first-in-class oral kinase inhibitor, produced durable responses in platinum-pretreated patients with EGFR exon 20 insertion–positive metastatic non–small cell lung cancer (NSCLC). The...
The combination of the KRAS inhibitor sotorasib with afatinib, a pan-ErbB tyrosine kinase inhibitor, was feasible in treating patients with non–small cell lung cancer (NSCLC) and mutated KRAS whose disease had progressed on prior therapies, including KRAS inhibitors alone, according to interim...
In a study reported in the Journal of Clinical Oncology, Devarakonda et al found that never-smokers with lung adenocarcinoma had a high frequency of RTK/RAS/RAF pathway driver alterations—similar to smokers with lung adenocarcinoma—but also harbored a significantly higher total frequency of...
In a study reported in the Journal of Clinical Oncology, Sabnis et al analyzed characteristics of genomically targeted single-patient use requests for investigational agents for the treatment of pediatric cancers. These requests were made from pediatric cancer programs over a 5-year period. As...
Thomas Powles, MD, PhD, of Queen Mary University of London, discusses phase II results from the NORSE study, which showed that the kinase inhibitor erdafitinib plus the monoclonal antibody cetrelimab produced meaningful responses in cisplatin-ineligible patients with first-line metastatic or locally advanced urothelial carcinoma and fibroblast growth factor receptor (FGFR) alterations (Abstract LBA27).
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...
PALB2 germline pathogenic variants are associated with a substantially increased risk for breast cancer and a smaller increased risk for pancreatic and ovarian cancers, warranting enhanced surveillance and the option of risk-reducing interventions, according to a global team of cancer genetic...
On October 7, the U.S. Food and Drug Administration (FDA) granted recognition to a partial listing of the Memorial Sloan Kettering Cancer Center Oncology Knowledge Base (OncoKB) as the first tumor mutation database to be included in the Public Human Genetic Variant Databases. The FDA recognized a...
Jenny F. Seligmann, MBChB, PhD, of the University of Leeds, discusses phase II findings that suggest adavosertib improved progression-free survival, compared with active monitoring, by inhibiting the WEE1 kinase in patients with RAS- and TP53-mutant metastatic colorectal cancer. In the trial, adavosertib’s activity tended to be even greater in left-sided tumors (Abstract 382O).
As reported in JAMA Oncology by Andrew X. Zhu, MD, PhD, and colleagues, the final overall survival analysis of the pivotal phase III ClarIDHy trial showed prolonged overall survival with ivosidenib vs placebo in previously treated patients with unresectable or metastatic cholangiocarcinoma and an...
In the German phase II PANAMA trial reported in the Journal of Clinical Oncology, Modest et al found that the addition of the monoclonal antibody panitumumab to fluorouracil (5-FU)/leucovorin maintenance therapy improved progression-free survival in patients with RAS wild-type metastatic colorectal ...
As reported in the Journal of Clinical Oncology by Seligmann et al, the phase II FOCUS4-C trial has shown activity of the WEE1 kinase inhibitor adavosertib in patients with TP53- and RAS-mutant metastatic colorectal cancer with disease control after first-line chemotherapy. As state by the...
The U.S. Food and Drug Administration (FDA) has granted approval of a new indication for cetuximab (Erbitux) in combination with encorafenib (Braftovi) for the treatment of adult patients with metastatic colorectal cancer and a BRAF V600E mutation, as detected by an FDA-approved test, after prior...
In a single-center phase II trial reported in the Journal of Clinical Oncology, Elamin et al found that the tyrosine kinase inhibitor poziotinib showed activity in previously treated patients with HER2 exon 20–mutant advanced non–small cell lung cancer (NSCLC). As related by the investigators,...
In a multicenter cohort study reported in JAMA Oncology, Hsu et al found that among pancreatic cancer kindreds, individuals with germline ATM pathogenic variants had a sixfold increased risk of developing pancreatic cancer vs noncarriers of pathogenic variants. Study Details The study involved data ...
Robin Cornelissen, MD, PhD, of Erasmus University in Rotterdam, discusses phase II findings from the ZENITH20-4 study, which explored the question of whether poziotinib could benefit patients whose newly diagnosed non–small cell lung cancer harbors EGFR and HER2 exon 20 mutations. Potentially, this novel tyrosine kinase inhibitor may fill an unmet medical need (Abstract LBA46).
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...
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 ...
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...
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...
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...
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...
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...
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...
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 ...