MD Anderson Research Highlights for September 28, 2022

Featuring cancer survivorship studies, new combination therapies for breast cancer and leukemia, and an analysis of RAS mutations in AML

MD Anderson News Release September 27, 2022

The University of Texas MD Anderson Cancer Center’s Research Highlights provides a glimpse into recent basic, translational and clinical cancer research from MD Anderson experts. Current advances include an investigation into the efficacy of dexamethasone for dyspnea relief, a combination therapy for hairy cell leukemia, an analysis of RAS mutations and their prognostic value in acute myeloid leukemia (AML), a possible new combination therapy for basal-like breast cancer, and swallowing exercises to improve the quality of life for patients with head and neck cancer undergoing radiotherapy. 

Trial finds dexamethasone should not be given for dyspnea relief in patients with cancer  
Limited evidence is available to support the use of systemic corticosteroids for relieving dyspnea, or shortness of breath, in patients with cancer. Led by David Hui, M.D., researchers examined the effect of high-dose dexamethasone on cancer-related dyspnea. A total of 149 ambulatory patients were enrolled in the trial and randomly assigned to receive 8 mg of dexamethasone or matching placebo capsules for 14 days. The primary outcome was an average change in dyspnea intensity of -1.6 in the dexamethasone and placebo groups. Trial data suggest high-dose dexamethasone did not significantly improve dyspnea compared to placebo and that it should not be routinely given to unselected patients with cancer. Read more on the findings in The Lancet. 

Dabrafenib plus trametinib shows durable responses in patients with relapsed/refractory BRAF V600E mutation-positive hairy cell leukemia 
First-line treatments for BRAF V600E mutation-positive hairy cell leukemia (HCL) are often effective, but the options for patients with relapsed or refractory HCL remain limited. In an open-label, Phase II trial, co-investigators Farhad Ravandi-Kashani, M.D., and Vivek Subbiah, M.D., evaluated the combination of dabrafenib plus trametinib in 55 HCL patients as part of the ongoing Rare Oncology Agnostic Research (ROAR) basket trial in patients with BRAF V600E mutated rare cancers. The combination had an objective response rate of 89% in HCL, with 65.5% of patients achieving a complete response. The most common adverse events were pyrexia (58.2%), chills (47.3%) and hyperglycemia (40%). The 24-month duration of response was 97.7%, with progression-free survival and overall survival rates of 94.4% and 94.5%, respectively. These durable responses and manageable safety profile led the authors to conclude that dabrafenib plus trametinib should be considered a therapeutic option for these patients. Learn more in Blood.

Comprehensive analysis of AML subtypes elaborates on impact of RAS mutations  
Acute myeloid leukemia (AML) is an aggressive form of leukemia, with multiple factors impacting overall prognosis. RAS mutations — which alter important signal pathways involved in growth and proliferation — have been linked to resistance in several targeted therapies, but their prognostic indication is unclear. To better understand this connection, researchers led by Tapan Kadia, M.D., conducted a comprehensive retrospective analysis in 1,420 patients with newly diagnosed AML, examining multiple factors to categorize various AML subtypes using newer sequencing techniques. They found that, while not independently prognostic, patients with RAS mutations tended to be younger, respond better to cytarabin-based chemotherapy and had better overall survival compared to patients with AML that did not have RAS mutations. They also discovered concomitant mutations, chromosome abnormalities, and that the type of therapy used played an important role in determining overall survival, treatment response and resistance. Learn more in the American Journal of Hematology.

Study identifies potential combination therapy to better target basal-like breast cancer  
Patients with aggressive basal-like breast cancer have limited treatment options and eventually develop drug resistance, highlighting a need for effective combination therapies. BET proteins are epigenetic regulators for multiple oncogenic genes, suggesting BET inhibitors merit further exploration as potential therapeutic strategies. Researchers led by Gonghong Yan, Ph.D., and Anil Korkut, Ph.D., used an integrated approach to study the effects of BET inhibition on breast cancer cells. They demonstrated that cells under BET inhibition upregulate the MCL1 protein, which is known to prevent cell death and is associated with poor prognosis and drug resistance when amplified. Upregulating MCL1 also made cells more vulnerable to MCL1 inhibition, highlighting the potential of combining BET and MCL1 inhibitors to improve treatment response in patients with elevated MCL1. Learn more in Cell Reports.  

Oral intake and swallowing exercises during radiotherapy associated with favorable functional outcomes 
Patients undergoing radiotherapy (RT) for head and neck cancers often experience ongoing challenges eating and swallowing. A new study led by Carly Barbon, Ph.D., and Katherine Hutcheson, Ph.D., expands on previously published work showing improved long-term outcomes when patients continue to eat or to exercise the swallowing muscles during RT. In this prospective cohort of 595 patients, both eating and exercising swallowing muscles during RT showed independent benefits related to shorter subacute feeding tube duration, better quality of life and less severe swallowing impairment (dysphagia). Within six months following treatment, patients who adhered to exercise using swallowing therapy were almost three times more likely to eat a solid diet, while patients who maintained full oral intake were twice as likely to eat a solid diet. Learn more in JAMA Otolaryngology.

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