Tag: Academic research

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FDA Approves Datroway as First-Line Therapy for Triple-Negative Breast Cancer

AstraZeneca and Daiichi Sankyo have received FDA approval for Datroway (datopotamab deruxtecan), an antibody-drug conjugate that offers an unprecedented improvement in survival to a patient population with no treatment options beyond chemotherapy. 

“Datopotamab deruxtecan is the first and only medicine to significantly prolong overall survival in the first-line setting compared to chemotherapy in patients with metastatic triple-negative breast cancer who are not candidates for immunotherapy,” said Tiffany A. Traina, MD, medical oncologist at Memorial Sloan Kettering Cancer Center. “This approval will bring a much-needed treatment option for these patients.”

Datroway is an antibody-drug conjugate (ADC) that targets the TROP2 protein, which is broadly expressed in several types of solid tumors and is associated with an increased risk of tumor progression and lower survival rates in breast cancer patients. With this approval, the ADC is now commercially available in the U.S. for three indications, including HR+/HER2– breast cancer and EGFR-mutated non-small cell lung cancer. Regulators across the world are now reviewing applications to expand this approval to Australia, Canada, China, the EU, Singapore, and Switzerland. 

The FDA decision is based on Phase III results from the TROPION-Breast02 clinical trial, where Traina was one of the investigators. In this trial, Datroway improved the median overall survival by five months and reduced the risk of disease progression or death by 43% compared to chemotherapy as a first line treatment. The ADC also achieved an objective response rate of 64% compared to 30% for chemotherapy. 

“Triple-negative breast cancer is notoriously difficult to treat,” said Dave Fredrickson, executive vice president of the oncology hematology business Unit at AstraZeneca. “Patients with metastatic disease, especially those who are unable to receive immunotherapy, urgently need more effective, durable and tolerable treatment options, which extend survival. With today’s approval, we are proud to bring Datroway to a broad population of advanced triple-negative breast cancer patients and we continue to study its promise as a mainstay treatment across tumors, stages, and settings.”

Accounting for about 15% of all cases of breast cancer, triple-negative breast cancer is the most aggressive type of breast cancer, with only 15% of patients surviving five years after their diagnosis. Because it doesn’t express any of the three most common targets for established breast cancer treatments, patients with triple-negative breast cancer have limited treatment options. 

Those patients whose tumors express PD-L1 are eligible to receive checkpoint inhibitor immunotherapy as a first line treatment in addition to chemotherapy. However, as many as 70% of patients with metastatic triple-negative breast cancer are not eligible for this form of immunotherapy, whether because their tumors do not express PD-L1 or because of comorbidities. 

“For seven out of 10 patients with metastatic triple-negative breast cancer who are not candidates for immunotherapy, chemotherapy has remained the only treatment option,” said Arlene Brothers, executive director of the Triple Negative Breast Cancer Foundation. “Today’s approval of Datroway means that for the first time, these patients will have a new standard of care beyond traditional chemotherapy at the outset of their treatment.”

The post FDA Approves Datroway as First-Line Therapy for Triple-Negative Breast Cancer appeared first on Inside Precision Medicine.

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The triple-hit hypothesis of Alzheimer’s disease: blood–brain barrier breakdown, infection, and neuroimmune activation as a unified etiological framework

Studies of Alzheimer’s disease (AD) have long been dominated by the amyloid cascade hypothesis, although mounting evidence suggests that amyloid-β (Aβ) deposition might be a late downstream event, rather than the initiating trigger of AD. Here, I propose a unifying Triple-Hit Hypothesis in which AD develops through a sequential interaction among three causative processes that have been individually implicated before in the onset of Alzheimer’s disease: (1) early blood–brain barrier (BBB) breakdown, (2) entry or reactivation of microbial agents within the brain, and (3) maladaptive innate immune responses that produce chronic neuroinflammation and Aβ accumulation. Converging data from human imaging, neuropathology, infectious disease studies, genetics, and vascular medicine could suggest that these three processes, which were in some previous studies linked to AD, might not be independent but rather that their temporal synergy could drive disease progression. This new conceptual framework integrates long-standing but fragmented lines of evidence and, if confirmed by experimental studies, offers the possibility for the development of new diagnostic biomarkers, new therapeutic entry points, and prevention strategies for AD. I argue that understanding AD as a disorder of the blood-brain barrier, immunity, and host–pathogen interactions should be taken into account in future research on the etiology and clinical progression of AD.
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Reading speed, visual deficits, and cerebral white matter integrity in veterans with and without mild traumatic brain injury

IntroductionSince 2001, approximately 17.3% of enlisted personnel have experienced a traumatic brain injury (TBI) according to the United States military. Visual deficits (e.g., convergence insufficiency or pursuit abnormalities) are reported as chronic, persistent symptoms of TBI, which can impact daily activities such as reading, computer work, and driving.MethodsIn the present study, diffusion-weighted imaging (DWI) data and behavioral and survey data related to visual function were analyzed for 63 combat veterans with and without mild TBI (mTBI). We also tested the hypothesis that white matter damage, measured as either decreased fractional anisotropy of white matter or “potholes” evident in the DWI data, would predict visual behaviors (reading speed, smooth pursuit catch-up saccades, and/or convergence insufficiency).ResultsOur key finding is that scores on the Convergence Insufficiency Symptom Survey (CISS) predicted whether the use of a color overlay would increase reading speed for participants with mTBI, but not for control participants. General linear model analyses found a relationship between smooth pursuit catch-up saccades and the cumulative number of white matter “potholes” found in white matter across the cerebrum. However, the sample size was too small to conclude that these correlations were uniquely related to TBI status.DiscussionThese findings point toward the importance of additional research to determine exactly how mTBI is associated with reduced reading speed and why altering the color of the page improves performance for individuals with mTBI and convergence insufficiency.
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Beyond the auditory: anxiety bridges sleep disturbances and depressive symptoms to tinnitus handicap

BackgroundTinnitus is closely associated with psychological factors including anxiety, depression, and sleep disturbances. However, how these variables interact to influence tinnitus severity remains poorly understood, warranting further exploration.MethodsThis retrospective study analyzed data from 285 patients with tinnitus, utilizing the Tinnitus Handicap Inventory (THI), Self-Rating Depression Scale (SDS), Self-Rating Scale of Sleep (SRSS), and Self-Rating Anxiety Scale (SAS) as assessment instruments. Univariate and multivariate regression analyses were performed to identify psychosocial factors associated with THI scores. Structural equation modeling (SEM) was employed to examine the mediating role of anxiety—specifically, whether sleep disturbances and depression exacerbate tinnitus handicap indirectly through heightened anxiety. Subgroup analyses were further conducted to evaluate the stability of this psychological mediation pathway across different demographic and clinical subgroups (e.g., age, gender, disease duration).ResultsTinnitus severity was significantly positively correlated with scores on the SRSS, SDS, and SAS (all P < 0.05). Multivariate regression analysis identified age, sleep quality (SRSS), and anxiety (SAS) as independent predictors of increased Tinnitus Handicap Inventory (THI) scores. Structural equation modeling further confirmed that SAS partially mediated the relationship between SRSS and THI (mediation effect: 31.7%) and fully mediated the relationship between SDS and THI. Subgroup analyses revealed that the mediating effect of anxiety was more pronounced in middle-aged and elderly individuals, females, and patients with left-sided tinnitus.ConclusionAnxiety serves as a central mediating mechanism linking sleep disturbances and depressive symptoms to tinnitus severity. The present findings demonstrate that anxiety not only directly exacerbates tinnitus-related handicap but also mediates the influence of sleep and mood disturbances on tinnitus distress. These findings underscore the critical role of anxiety in personalized tinnitus treatment.
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Does the phubbing scale measure the same construct across sexes? Evidence from a Nigerian sample

IntroductionPhubbing is associated with excessive use of digital technologies, and the Phubbing Scale (PS) is widely used to measure it. The PS may be influenced by cultural variations, so it is advisable to validate it before applying it in a new cultural context. Phubbing has emerged as a construct of interest in Nigeria, yet no validation studies for the PS have been conducted in this population.MethodsTo address this gap, the PS, along with scales measuring technological addictions and digital life balance, was administered to 396 Nigerian university students (18 to 25 years old; 80.6% female). Confirmatory Factor Analysis was used to test two 10-item models and one 8-item model. The best-fitting model was subsequently tested. Internal and external validity, and measurement invariance across sexes were assessed.ResultsThe 8-item correlated two-factor model (PS-8) showed the best results. For PS-8, internal and external validity, and strict measurement invariance across sexes were supported based on global fit indices. However, parameter estimates suggested potential sex-related differences in the construct. In females, factor loadings and the correlation between factors were adequate, whereas in males several items of Factor 2 showed low loadings, and the correlation between factors was negligible.ConclusionIn conclusion, the PS-8 appears suitable for measuring phubbing in this population, although potential sex-related differences should be considered. These differences may stem from psychometric limitations in the Smartphone Obsession factor items and/or from variations in how the PS construct manifests across sexes, which could affect interventions or comparative studies. Considering the limitations of the study, future research will be necessary to corroborate these findings.
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Association between neurodegenerative plasma biomarkers and geriatric depression in older adults with and without clinical dementia in Kinshasa, Democratic Republic of the Congo

IntroductionPrevious Western studies have shown an association between neurodegenerative plasma biomarkers and geriatric depression. However, few studies have examined this relationship in sub-Saharan African countries. This article examines this association in older adults with or without clinical dementia in Kinshasa, Democratic Republic of Congo.MethodsThis cross-sectional study included eighty-one people aged 65 years and older assessed for dementia using the Community Dementia Screening Instrument (CSID) and the Alzheimer’s Disease Questionnaire. Depression and cognitive impairment were assessed using the Geriatric Depression Scale and the African Neuropsychological Battery (ANB), respectively. Plasma biomarkers measured included β-amyloid (Aβ) 40/42, phosphorylated tau 181 (p-tau), neurofilament light chain (NfL), glial fibrillar acid protein (GFAP), interleukins (IL-1β, IL-10), and tumor necrosis factor-α (TNF-α). Logistic regression models were used to estimate the likelihood that these biomarkers are associated with depression, adjusting for sex, age, and education level.ResultsThe mean age of the participants was 72.9 years. Of those suspected of suffering from Alzheimer’s disease (AD), 80% had geriatric depression. High blood pressure was common in participants with suspected AD (60%). People with dementia had significantly lower cognitive scores on all ANB tests than those without dementia. GFAP and NfL were significantly associated with higher odds of geriatric depression, with odds ratios of 1.98 (1.17–3.67; p = 0.02) and 1.76 (1.06–3.20; p = 0.04), respectively. Other biomarkers were not associated with depression.ConclusionThis study suggests a potential role of nonspecific biomarkers of AD, neurodegeneration, and astrocytic glial activation in geriatric depression in older adults in sub-Saharan Africa.
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Unseen intimate partner violence: regional differences in controlling behaviours

IntroductionControlling behaviour is considered a form of emotional abuse and restricts an individual’s autonomy. This study aims to determine the factors associated with women’s exposure to controlling behaviour by their spouse/partner in the last year, as of the time the survey was conducted, by place of residence in Türkiye.MethodsThis study utilised microdata obtained from the National Research on Domestic Violence against Women in Türkiye. Binary logistic regression analysis was employed to determine the factors associated with women’s exposure to controlling behaviour by their spouse/partner.ResultsThe results of the study showed that age, educational level, the woman’s greater contribution to household income, suicidal thoughts, previous pregnancies, the educational level of the spouse/partner, whether or not the man beating his wife is considered acceptable, the educational level of the spouse/partner, fear of the spouse/partner, the spouse/partner fighting with the man in a way that involves physical violence, the spouse/partner experiencing physical violence from their own family, exposure to other types of violence by the spouse/partner, knowledge of preventive measures against violence, and household size were found to be associated with exposure to controlling behaviour.DiscussionThe study found that the significance and effect of variables related to exposure to controlling behaviour also differed by women’s place of residence. According to the study, appropriate strategies to reduce controlling behaviour should be developed, taking into account public health programmes to raise awareness of controlling behaviour towards women, based on their place of residence, and considering the determinants that influence exposure to controlling behaviour.
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STAT+: EU and US advisers split over AstraZeneca breast cancer drug 

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Merck’s bet on an antibody-drug conjugate developed in China has paid off in a major Phase 3 lung cancer study, where sacituzumab tirumotecan paired with Keytruda sharply outperformed Keytruda alone in a subset of lung cancer patients.

Also, the NIH is down another leader, and Sam Altman-backed longevity startup Retro Biosciences raises more funds.

Continue to STAT+ to read the full story…

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STAT+: Pharmalittle: We’re reading about a Parkinson’s drug setback, a Merck lung cancer therapy, and more

And so, another working week will soon draw to a close. Not a moment too soon, yes? This is, you may recall, our treasured signal to daydream about weekend plans. Our agenda is unusually busy thanks to a lengthy to-do list that must be tackled before we walk one of the no-longer-so-short people down the aisle. What else? Hard to keep track, but once the chaos subsides, we hope to settle in for another listening party, where the rotation will likely include this, this, this, this and this. And what about you? Spring is in the air, so perhaps this is time to hike a trail, stroll through a park, or take a long drive to nowhere. You could also plan a summer getaway (book now before those fuel costs rise again) or clear out the perennial clutter. If all this is too much or the weather fails to cooperate, you could simply go into zen mode and plan the rest of your life. Well, whatever you do, have a grand time. But be safe. Enjoy, and see you on Tuesday, since there is a long weekend due to a holiday on this side of the pond. …

Biogen and Denali Therapeutics said Thursday that their experimental therapy for Parkinson’s disease failed to slow the degenerative brain disorder in a randomized trial, dealing a substantial blow to a scientific approach that stoked excitement among advocates and academics, STAT explains. In the study, 648 adults with Parkinson’s were randomized to receive either a placebo or a pill targeting a protein called LRRK2. In 2004, researchers discovered that mutations in the LRRK2 gene can cause a rare, inherited form of Parkinson’s. And in 2018, another group of scientists showed that blocking the protein might actually benefit all patients with the disease. The results are a significant setback to the latter idea.

Earlier this month, Genentech offered countless academics and other researchers up to $125,000 in grants to generate papers about several topics that read like key talking points for a trip to Capitol Hill, STAT reports. The company is seeking “rigorous, independent” work that focuses on the potential consequences of U.S. pricing policies on future innovation, the idea that pharmaceutical discovery is a strategic national asset, and the risks surrounding R&D, according to a request for proposals that came with a June 30 deadline for submissions. Such overtures are hardly new, but this particular solicitation appears notable partly because the company is being very direct about seeking research that is designed to address specific points, rather than solicit topics that may — or may not — dovetail with corporate goals.

Continue to STAT+ to read the full story…