Latest news with #ClinicalTrials
Medscape
22-05-2025
- Health
- Medscape
Conference MDAngle: ASCO 2025 Early Breast Cancer
Preconference Considerations ASCO 2025: Previewing Updates in Early-Stage Breast Cancer Dr Chavez MacGregor eagerly awaits the 2025 ASCO Annual Meeting, especially the sessions on early-stage breast cancer. She highlights new data on treatment optimization for HER2-positive disease and updates on managing HR-positive breast cancer in premenopausal women, including results from key trials like SOFT, TEXT, and ASTRRA. Dr Chavez MacGregor is also looking forward to sessions on circulating tumor DNA and emerging therapies for improving quality of life during endocrine treatment. Quick Clinical Takeaways Coming soon: Dr Chavez MacGregor will share new data and insights on early breast cancer directly after ASCO. How Will My Patients Benefit? Coming soon: Reflections from Dr Chavez MacGregor on how new data from ASCO will affect her patients with early breast cancer. Lead image: Medscape
Yahoo
20-05-2025
- Health
- Yahoo
CAR-T cell therapy is revolutionising cancer treatment – here's how it works
Personalised medicine is already a reality in clinical practice, and CAR-T cell therapy is one of its most promising tools. This innovative approach, which involves genetically modifying the cells of the immune system, is transforming the way we treat not only cancer, but also other diseases. The CAR-T revolution is widely documented, with more than 1,000 clinical trials currently underway worldwide according to the ClinicalTrials platform. This reflects an enormous amount of scientific and medical interest. To understand why it is of such interest, we first need to know what the function of a T-lymphocyte is. These cells belong to the immune system, and are responsible for finding and eliminating cells that are infected or have become abnormal, such as cancerous cells. We can think of them as the body's police force: they recognise when something is wrong, and help to maintain the balance in our body. CAR-T cells are, in essence, T-lymphocytes equipped with a next-generation membrane receptor: a structure specifically designed to recognise and attack tumour cells with a precision and sensitivity far superior to a normal T-cell. The difference is huge, like going from a mid-2000s Nokia phone to the latest iPhone. Thanks to this modification, CAR-T cells can generate an immune response up to 1,000 times stronger than an ordinary lymphocyte. This makes it possible to eliminate cancer cells that do not respond to conventional treatments. But what exactly is this alteration that proves so lethal to cancer cells? CAR-T cells are designed as 'reconnaissance and attack' against cancer, and to do this, they have three main components. There is an external part that acts like a radar, identifying tumour cells; another part that passes through the cell membrane to transmit the signal inwards, and an internal part that triggers the T-cell response, activating its attack. Although this basic design has already proven very powerful, researchers continue to improve it, both to make it even more effective and to prevent cells from becoming exhausted before they are able to kill off every last tumour cell. Therapeutic options for many patients have multiplied thanks both to the ability to develop these cells ex vivo – in the laboratory – and to advances in gene editing. To date, there are 7 CAR-T therapies which are authorised for use in patients. Despite their efficacy, these therapies are not yet available to all patients due to their high cost and associated risks. This underlines the need to improve both their safety and accessibility. Moreover, although CAR-T has been very successful in treating leukaemias and myelomas, its application in solid tumours remains a challenge. In these cases, the tumour microenvironment imposes additional barriers: T cells must pass through dense matrices that hinder their motility. The acidic environment also compromises their functionality, and nutrient shortages can lead to cellular exhaustion. Such factors have so far limited the success of CAR-T therapies in solid tumours, but researchers continue to explore new ways to overcome these difficulties. One such method involves combining chemotherapy and radiotherapy to enable T-cells to reach tumour cells. Combining CAR-T with immune checkpoint inhibitors – drugs that block certain signals used by tumour cells to avoid being attacked by the immune system – could also improve their effectiveness in such hostile environments. However, it is not always possible to obtain lymphocytes from the patient, either due to limitations in quality or quantity or clinical conditions that make collection difficult. To address this, research is being done into allogeneic therapies that use 'off the shelf' CAR-T cells. These use T-cells from healthy donors, and are stored ready for use when needed. These methods not only reduce production times and costs, but also expand access to such treatments to a wider range of patients. Although there are still several hurdles to overcome, the main challenge is the expanding the application of CAR-T cells to other cancers, especially solid tumours, which could benefit from these therapies. Examples include glioblastoma and metastatic ovarian cancer. In the case of glioblastoma (a type of brain tumour), specific targets such as B7H3 or EGFRvIII are being investigated. These antigens are only expressed on tumour cells, improving the accuracy of these therapies. Also under study are new delivery modes that cross the blood-brain barrier (a barrier that regulates the passage of what can and cannot reach the brain) and ways to modulate inflammation, which is critical in treating brain tumours. For metastatic ovarian cancer, for which there is currently no curative treatment, CAR-Ts offer a promising alternative. Clinical trials have shown encouraging results by targeting certain new tumour markers. Moreover, CAR-T therapies are not only being applied in oncology. They are also being investigated for use in the treatment of autoimmune diseases, with trials underway for diseases such as rheumatoid arthritis. This opens up new possibilities for the future use of these therapies. CAR-T's advances, both consolidated and those on the horizon, have led the pharmaceutical industry to boost its investment in these therapies. Currently, the CAR-T cell therapeutics market is estimated to grow from $10.39 billion in 2024 to $128.55 billion in 2032. The true potential of these therapies is yet to be discovered, and may lie in their effective application against solid tumours. However, one thing is for certain: what until recently seemed a futuristic concept is now a reality. Personalised medicine is here to stay, and CAR-T therapies are leading the way. Este artículo fue publicado originalmente en The Conversation, un sitio de noticias sin fines de lucro dedicado a compartir ideas de expertos académicos. Lee mas: Joe Biden has prostate cancer with bone spread – an oncologist explains what you need to know How 7,000 steps a day could help reduce your risk of cancer How optical fibres are transforming cancer care Lydia Begoña Horndler Gil no recibe salario, ni ejerce labores de consultoría, ni posee acciones, ni recibe financiación de ninguna compañía u organización que pueda obtener beneficio de este artículo, y ha declarado carecer de vínculos relevantes más allá del cargo académico citado.
Daily Mail
14-05-2025
- Health
- Daily Mail
SARAH VINE: I have tried all the weight loss jabs from Ozempic to Wegovy to Mounjaro... and THIS is the one that's easily the best
Every age has its great rivalries: Rome vs Carthage, Mozart vs Salieri, Shakespeare vs Marlowe, the Rolling Stones vs The Beatles. For us, halfway through the 2020s, it's Mounjaro vs Ozempic, the battle of the fat jabs. In the first ever head-to-head clinical trial, tirzepatide (the active ingredient in Mounjaro) has been found to be almost 50 per cent more effective than semaglutide (the active ingredient in Ozempic and Wegovy).
Medscape
06-05-2025
- Health
- Medscape
CABG Still Superior to Stents Despite FAME 3 Endpoint Swap
What happened with the 5-year FAME 3 results is not right. The reporting of this trial comparing stenting vs coronary artery bypass graft surgery (CABG) in patients with multivessel coronary artery disease (CAD) defies proper scientific principles. The FAME 3 Trial of Stents vs Surgery FAME 3 tested the best strategy to revascularize patients with multivessel CAD. Three previous trials comparing percutaneous coronary intervention (PCI) vs CABG (SYNTAX, FREEDOM, and BEST) had all found surgery to be superior. But both technologies had advanced, perhaps PCI more than CABG. PCI is now done via the radial artery, dramatically reducing bleeding complications. What's more, the use of fractional flow reserve (FFR) to assess stenosis severity should ensure that drug-eluting stents are placed only in hemodynamically significant lesions. FAME 3 was conducted because it was now possible that PCI could prove equal to CABG. It was designed and powered as a 1-year noninferiority trial with follow-up at 3 and 5 years, 'if funding allows.' Original 1-Year Results The 1-year results were clear. The primary endpoint of all-cause death, myocardial infarction (MI), stroke, and repeat revascularization occurred in 10.6% of patients in the PCI group and 6.9% of those in the CABG group. The 50% higher rate of events with stenting had an upper bound of 2.2, which was well over the prespecified noninferiority margin of 1.45. (HR = 1.5; 95% CI, 1.1-2.2). Three components of the composite endpoint — death, MI, and repeat revascularization — were numerically higher in the PCI arm. The authors concluded that contemporary FFR-guided PCI was not noninferior to CABG at 1 year. The title of the accompanying editorial was "CABG versus PCI — End of the Debate?" The writer answered his own question in the affirmative. The FAME 3 trial bolsters the role of CABG as the benchmark for patients with multivessel coronary disease. "Bolster" is the correct verb because FAME 3 clearly corroborated the three previous trials. 3-Year Results and an Endpoint Change Then something happened. The FAME 3 investigators used a different endpoint (death, MI, and stroke) in reporting the 3-year results. Repeat revascularization was dropped. The result of this change was that the 30% higher rate of events in the PCI arm did not reach statistical significance (12% vs 9.2%; HR = 1.3; 95% CI, 0.98-1.83; P =.07). But if they had stuck to their original primary endpoint, the 3-year result would have been similar to the 1-year result. In fact, the accrual of more events from year 1 to 3, particularly in the stent arm (18.6% vs 12.5% for surgery), led to more confidence in this endpoint, as evidenced by tighter confidence intervals (HR = 1.5; 95% CI, 1.2-2.00; P =.002). The change in endpoint prompted the authors to now conclude there was 'no difference' in major adverse events between FFR-guided PCI and CABG. 5-Year Results The authors continued with their new endpoint for the 5-year results. Now, 16% of patients in the PCI arm experienced either death, MI, or stroke vs 14.1% in the CABG arm. The higher rate of events in the PCI arm did not reach statistical significance (HR = 1.16; 95% CI, 0.89-1.52; P =.27). If they had used the original primary endpoint that includes repeat revascularization, CABG would have been superior (25% vs 18% for CABG; HR = 1.44; 95% CI, 1.15-1.81). More events meant even tighter confidence intervals. The rates of MI and repeat revascularization were also higher after PCI. The authors once again ignored the trial's original endpoint and concluded that there was no difference in the death/MI/stroke endpoint. They also noted that a landmark analysis looking at years 2-5 found no accrual of benefit in the surgery arm. The results were presented at the 2025 American College of Cardiology scientific sessions where the lead sentence of the press release noted that 'in contrast to previous studies patients with severe triple-vessel heart disease fared equally well whether they underwent CABG or PCI.' Headlines in news coverage implied that stents had closed the gap and were equivalent to surgery. Comments To conclude that the two therapies were similar required a different endpoint that omitted repeat revascularization. Had the authors kept the original endpoint, FAME 3 at 5 years would have drawn a similar conclusion to the 1-year results and the three previous trials: CABG is superior to PCI for patients with multivessel CAD. I will make three arguments why this endpoint change and revised conclusion were inappropriate: First, repeat revascularization is a relevant clinical outcome. The authors obviously believed so because they chose to include it in the composite primary endpoint for the 1-year outcome. What's more, two observational studies have associated repeat revascularization with higher mortality. This makes sense because the rate of MI in the PCI arm of FAME 3 at 5 years was 60% higher than for surgery, so many of these repeat procedures probably were done for acute coronary syndrome. Second, changing the endpoint is improper science. The authors may argue that the change was prespecified, but I see no clinical reason why the PCI-vs-CABG question requires different endpoints at different follow-up times. The third reason that use of fewer events in the revised endpoint is problematic relates to statistical rules. The authors list as their first limitation that FAME 3 was not powered for secondary endpoints. Indeed the confidence intervals for the revised endpoint were wide and included the chance that PCI was more than 50% worse. What's more, the secondary endpoint of death, MI, and stroke was not adjusted for multiple comparisons, further introducing uncertainty. Conclusion My take-home is that while PCI and CABG have improved over time, CABG remains the superior strategy in patients with multivessel disease. The findings for FAME 3 at 5 years are no different from the 1-year outcomes. The only change has been in how the authors presented the results.
Yahoo
06-03-2025
- Health
- Yahoo
Why I'm sounding the alarm on the next puberty blockers scandal
Few issues in contemporary medicine have generated as much controversy as the use of puberty blockers in gender distressed children. The Government, responding to the findings of the Cass Review, has rightly banned the prescription of these drugs. Many other countries have, too. However the Government last week announced an £11 million clinical trial of these medicines to gather evidence of their effects. This raises a fundamental question: can a clinical trial of puberty blockers on children experiencing gender distress be done ethically? The answer, upon scrutiny, is a resounding 'no'. I have witnessed firsthand the grave dangers posed by the rush to medicalise childhood gender distress. As a former psychiatrist at the Tavistock and Portman NHS Trust, I was one of the whistleblowers who raised concerns about the practices at the now shuttered Gender Identity Development Service (Gids). What we uncovered was a service driven more by ideology than by robust clinical reasoning. Many distressed children, often same-sex attracted and with autistic comorbidities, were put on a medical pathway to transition by some clinicians who had been captured by 'trans' ideology and, as a result, cast aside ordinary sound clinical judgment. A clinical trial risks repeating these ethical failures. These trials are governed by rigorous ethical and legal standards, designed to protect participants from harm. The foundation of these standards is the Declaration of Helsinki, alongside the Good Clinical Practice guidelines and the UK's Medicines for Human Use (Clinical Trials) Regulations. These frameworks exist to ensure that the benefits of any new medical intervention outweigh the risks. The Cass Review has made it clear that the evidence base for the safety and effectiveness of puberty blockers is extraordinarily weak, and that their risks are significant. Existing studies suggest serious concerns, including negative impacts on bone density, cognitive development, and future sexual function. Further, over 95 per cent of children started on a medical pathway will proceed to cross sex hormones and many to surgical intervention. Thus starting any child on PBs is freighted with that knowledge, and of course the ethical implications of that knowledge. To be clear, the prescription of puberty blockers in the context of a trial would, in effect, introduce a known risk of systemic physical harm to a physically healthy child. To put it mildly, this is a divergence from normal clinical trial practice. One of the core principles of medical research is that a clinical trial must seek to answer a question that cannot be resolved by other means. Yet in the case of puberty blockers, safer research avenues remain unexplored. We should be conducting robust long-term follow-up studies of those who have already undergone such treatment, qualitative research into the experiences of the growing numbers of detransitioners, and further animal studies to understand the biological impact of these drugs on adolescent brain development. Another major ethical concern is the question of informed consent. Children under 16 cannot legally provide informed consent for a Clinical Trial of an Investigational Medicinal Product, meaning that parental consent would be required. Yet, given the politicised environment surrounding gender identity, it is difficult to see how true informed consent can be obtained. For example, parents, subjected to trans activist narratives claiming that refusal to provide puberty blockers increases their child's risk of suicide, will not be in a position to make a free and uncoerced decision. The argument that puberty blockers prevent suicide is completely unsubstantiated. For example, a recent Finnish study found no significant difference in suicide rates among youth diagnosed with gender dysphoria when adjusted for mental health comorbidities. In the UK, Professor Louis Appleby, the leading authority on suicide prevention, has called for caution on the use of false assertions as regard risk of suicide in this group . Informed consent is meaningless when it is obtained under conditions of misinformation and fear. There are moments in medical history when the imperative to 'pause and reflect' must override the drive to push forward. Now is one such moment. Given the absence of an established safety profile, the lack of high-quality evidence supporting their efficacy, and the well-documented risks, any such trial would violate our ethical and regulatory frameworks. The medical community, politicians, and regulators need to draw a line under this scandalous piece of medical history. Instead of experimenting on confused children with medical interventions that do more harm than good, we should be dedicating our resources to understanding and addressing the root causes of gender distress, researching psychosocial treatments and following up on the 9,000 children who went through Gids. Let us not repeat mistakes of the past. Dr David Bell is a retired consultant psychiatrist and was a Governor of the Tavistock and Portman NHS Foundation Trust Broaden your horizons with award-winning British journalism. Try The Telegraph free for 1 month with unlimited access to our award-winning website, exclusive app, money-saving offers and more.
