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This is Part 2 of The Evolving 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...
In a phase I/II trial (KRYSTAL-1) reported in The New England Journal of Medicine, Rona Yaeger, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues found that the KRAS G12C inhibitor adagrasib showed activity alone and in combination with cetuximab in heavily pretreated patients ...
Studies show that although clonal hematopoiesis is an age-related phenomenon in the general population, it can also be induced by exposure to chemotherapy, which can affect both the emergence and evolution of clonal hematopoiesis clones, accelerating aging at both the physiologic and molecular...
In a study from the Children’s Oncology Group reported in the Journal of Clinical Oncology, Abbou et al found that measuring circulating tumor DNA (ctDNA) in intermediate-risk rhabdomyosarcoma was feasible and that the presence of ctDNA prior to treatment was associated with poorer prognosis. As...
The EGFR tyrosine kinase inhibitor osimertinib may improve rates of disease-free survival and reduce the risk of recurrence in patients with resected, EGFR-mutant non–small cell lung cancer (NSCLC), according to a new exploratory analysis of the ADAURA trial published by Roy S. Herbst, MD, PhD,...
In a study reported in a letter to the editor in The New England Journal of Medicine, Mata et al found that U.S. individuals of African ancestry and Hispanic patients made up an increasing proportion of patients undergoing next-generation sequencing of tumor samples over a 9-year period ending in...
In a study reported in The Lancet Oncology, Wang et al identified mutations linked to high tumor mutation burden in microsatellite-stable (MSS) gastrointestinal cancers that may be associated with efficacy of immune checkpoint inhibitor therapy. Study Details Molecular alterations in 48,606...
As reported in The Lancet Oncology by Paolo A. Ascierto, MD, of the Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Pascale, Naples, and colleagues, the second interim overall survival analysis of the phase III IMspire150 trial has shown a numeric but...
In a study reported in the Journal of Clinical Oncology, Yadav et al estimated the risk of contralateral breast cancer among patients with invasive breast cancer and germline pathogenic variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2. Study Details The study population consisted of 15,104...
The field of precision oncology has become so complex that even experienced oncologists can find it challenging to decipher the molecular test results of tumor tissue and navigate treatment options for patients. Investigators revealed that a new program may aid gastrointestinal cancer physicians in ...
In a study reported in the Journal of Clinical Oncology, Sjöström et al identified a 16-gene signature—Profile for the Omission of Local Adjuvant Radiation, or POLAR—that predicted low likelihood of benefit from adjuvant radiotherapy in preventing locoregional recurrence in patients with...
On January 4, the U.S. Food and Drug Administration (FDA) approved FoundationOne Liquid CDx to be used as a companion diagnostic to identify patients with ROS1-positive non–small cell lung cancer (NSCLC) or NTRK fusion–positive solid tumors who do not have a tissue sample available and may be...
In a Chinese study reported in the Journal of Clinical Oncology, Sun et al developed a risk prediction model (BRCA-CRisk) to assess the risk of contralateral breast cancer in patients with breast cancer and BRCA1/2 pathogenic/likely pathogenic variants. Study Details The model was developed in a...
In a study reported in The Lancet Oncology, Garcia-Pelaez and colleagues found that presence of germline truncating pathogenic variants or likely pathogenic variants of CDH1 were associated with hereditary diffuse gastric cancer (HDGC) tumor risk syndrome–related cancer phenotypes (lobular breast...
On December 21, Foundation Medicine, Inc, announced that the U.S. Food and Drug Administration (FDA) approved its FoundationOne Liquid CDx as a companion diagnostic to identify patients with non–small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 L858R substitutions...
Even as they’ve revolutionized cancer treatment, immune checkpoint inhibitors have been shown to produce a range of adverse immune-related side effects. Researchers have now identified inherited genetic variations that may place patients at high risk for complications when undergoing treatment with ...
In a phase II trial reported in the Journal of Clinical Oncology, Fu et al found that the WEE1 kinase inhibitor adavosertib was active in patients with refractory solid tumors with CCNE1 amplification, with evidence of increased activity in epithelial ovarian cancer. Study Details In the trial, 30...
Richter syndrome is an aggressive lymphoma that develops in up to 1% of patients with chronic lymphocytic leukemia (CLL) and it serves as an example of histologic transformation. While recent advances have transformed the treatment landscape of CLL, Richter syndrome remains associated with poor...
On December 12, the U.S. Food and Drug Administration (FDA) granted accelerated approval to adagrasib (Krazati), a RAS GTPase family inhibitor, for adult patients with KRAS G12C–mutated, locally advanced or metastatic non–small cell lung cancer (NSCLC), as determined by an FDA-approved test, who...
Irene Roberts, MD, of Oxford’s Weatherall Institute of Molecular Medicine, discusses children with Down syndrome, who have a more than 100-fold increased risk of developing acute myeloid leukemia before their fourth birthday compared to children without Down syndrome. Their risk of acute lymphoblastic leukemia is also increased by around 30-fold. Dr. Roberts details current knowledge about the biologic and molecular basis of this relationship between leukemia and Down syndrome, the role of trisomy 21 in leukemogenesis, and the clinical implications of these findings.
Jiye Liu, PhD, of Dana-Farber Cancer Institute, discusses study findings that demonstrate KDM6A regulates CD38 and CD48 expression in multiple myeloma. Dr. Liu’s team validated combination treatment with an FDA-approved EZH2 inhibitor plus daratumumab, which can overcome daratumumab resistance in preclinical multiple myeloma models, providing the rationale for combination clinical trials to improve patient outcome (Abstract 148).
Francesco Maura, MD, of the University of Miami, Sylvester Comprehensive Cancer Center, discusses his team’s findings in which they defined a comprehensive catalogue of genomic determinants of response to DKRd (carfilzomib, lenalidomide, dexamethasone) in newly diagnosed multiple myeloma. The researchers have identified a number of new genomic alterations that explain resistance to the agents currently used in combination regimens (Abstract 470).
Smita Bhatia, MD, MPH, of the Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, discusses study findings that showed key somatic mutations in the peripheral blood stem cell product increases the risk of developing therapy-related myeloid neoplasms (Abstract 119).
Researchers from The University of Texas MD Anderson Cancer Center showed that inhibiting menin with an oral small-molecule inhibitor of the menin-KMT2A interaction, SNDX-5613—now named revumenib—yielded encouraging responses for patients with advanced acute leukemias and KMT2A rearrangements or...
Stephen M. Ansell, MD, PhD, and Patrizia Mondello, MD, PhD, both of the Mayo Clinic, discuss the 20% of patients with follicular lymphoma (FL) who relapse early and experience a poor prognosis. The researchers found that FLs with high levels of IRF4 expression are associated with a suppressive tumor microenvironment, and selective IRF4 silencing restores antilymphoma T-cell immunity. Further investigation is warranted to identify the mechanisms by which IRF4 controls tumor immunity to develop precision therapies for this population (Abstract 70).
Patients with invasive breast cancer who had low scores on an investigational gene molecular signature had similar rates of local recurrence independent of whether they received adjuvant radiation therapy after breast-conserving surgery, according to findings presented by Karlsson et al at the 2022 ...
My father was diagnosed with prostate cancer in 1994, when he was just 55 years old. He died 6 years later. The cancer was so aggressive, it took only a few weeks from the time he was diagnosed for the cancer to grow to the size of a softball, and even a radical prostatectomy couldn’t save his...
On December 1, the U.S. Food and Drug Administration (FDA) approved olutasidenib (Rezlidhia) capsules for adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test. The FDA also approved the Abbott RealTime IDH1...
More than 1.4 million patients were diagnosed with prostate cancer in 2020 globally, but the molecular characteristics of the disease remain unexplored for the majority of patients around the world. In the final days of the Movember campaign, which every year in November aims to raise awareness of...
As reported in JAMA Oncology by Schram et al, the phase IIb tumor-agnostic JAVELIN BRCA/ATM trial has shown that the combination of avelumab and talazoparib did not meet the prespecified objective response rate goal among patients with advanced BRCA1/2-altered or ATM-altered solid tumors. The...
Researchers have discovered the factors that may make breast and ovarian cancers associated with BRCA1 and BRCA2 gene mutations more likely to recur, according to new findings published by Shah et al in Nature Communications. These mutations are known to strongly predispose women to breast and...
In a study reported in JAMA Oncology, Reid et al found that undergoing prophylactic bilateral mastectomy was as common in women with breast cancer with pathogenic/likely pathogenic variants in ATM and CHEK2 (moderate-penetrance genes) as in those with variants in BRCA1, BRCA2, or PALB2...
In a single-institution analysis reported in the Journal of Clinical Oncology, Benjamin L. Lampson, MD, and colleagues found a higher prevalence of rare germline ATM variants in chronic lymphocytic leukemia (CLL) vs other lymphoid and myeloid disorders. They also determined that patients with CLL...
As reported in the Journal of Clinical Oncology by Gilberto de Castro, Jr, MD, PhD, and colleagues, 5-year follow-up of the KEYNOTE-042 trial showed a maintained overall survival benefit with first-line pembrolizumab vs chemotherapy in patients with non–small cell lung cancer (NSCLC) with a PD-L1...
“CodeBreaK 200 clearly establishes sotorasib as the new standard of care, replacing docetaxel as second- or third-line therapy for advanced KRAS G12C–mutated lung cancer,” stated invited discussant Natasha Leighl, MD, of the Princess Margaret Cancer Centre, Toronto. “Sotorasib improved...
The KRAS G12C inhibitor sotorasib doubled the rate of progression-free survival at 12 months and reduced the risk of disease progression or death by 34% compared with standard second-line docetaxel for patients with previously treated non–small cell lung cancer (NSCLC) and KRAS G12C mutations....
In a study reported in the Journal of Clinical Oncology, Grob et al found that next-generation sequencing detection of FLT3-internal tandem duplication (FLT3-ITD) measurable residual disease (MRD) in complete remission was associated with markedly increased risk of relapse and poorer overall...
In the NCI-MATCH trial, which matches new treatments to patients with cancer based on the genetic makeup of their tumors, 22% of patients with AKT1 E17K–mutant metastatic tumors treated with the AKT inhibitor ipatasertib saw their tumors shrink, according to a novel study published by Kalinksy et...
Researchers have found that a new drug may be able to target—and for the first time, inhibit—the function of the MYC gene. Until now, no other drug has been able to do this safely and effectively, according to findings from a phase I clinical trial published by Garralda et al in the European...
Early trials of the targeted oral drug repotrectinib discovered that it may help treat patients with a certain type of non–small cell lung cancer (NSCLC), according to a new study published by Cho et al in the European Journal of Cancer. The results of the TRIDENT-1 trial—presented at the 34th...
In a study reported in The Lancet Oncology, Qin et al found that the presence of mosaic chromosomal alterations detected in blood-derived DNA was associated with an increased risk of lung cancer among persons of Chinese and European heritage. Study Details The study involved two cohorts:...
Olaparib and adavosertib can be safely used to treat patients with cancers that are driven by certain mutations occurring in response to DNA damage if they are given in sequence rather than concurrently, according to a novel study published by Yap et al in the European Journal of Cancer. The...