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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 ...
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...