Latest news with #clinicalTrials
Medscape
a day ago
- Health
- Medscape
Key Highlights in Ovarian Cancer From ASCO 2025
Novel drug combinations that improve outcomes, outstanding questions about treatment sequence, and encouraging results in chemotherapy resistant disease are among the ovarian cancer highlights presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Stephanie Gaillard, from Johns Hopkins School of Medicine, Baltimore, Maryland, begins with the ROSELLA trial of relacorilant plus nab-paclitaxel vs nab-paclitaxel alone in patients with platinum-resistant ovarian cancer. The results showed improved progression-free survival (PFS) and overall survival (OS) in this difficult-to-treat population. Next, she discusses the TRUST trial in advanced ovarian cancer, comparing radical upfront surgical therapy followed by chemotherapy with neoadjuvant chemotherapy followed by surgery, followed by further chemotherapy. Although PFS was improved by upfront surgery, OS was not, leaving the treatment sequence open to question. Dr Gaillard then reports on an updated survival analysis from the OVATION-2 study of intraperitoneal IMNN-001 plus neoadjuvant chemotherapy in newly diagnosed advanced epithelial ovarian cancer. The approach achieved impressive OS, alongside the previously reported PFS benefit. Finally, she reports on a phase 2 study of pembrolizumab and lenvatinib in recurrent or persistent clear cell ovarian carcinoma. The combination showed encouraging response rates and PFS in a population known to be highly resistant to chemotherapy.
Medscape
2 days ago
- Health
- Medscape
Is One Fasting Method Better Than Another?
Various intermittent fasting strategies and calorie restriction diets similarly improved body weight compared with ad libitum diets; only alternate-day fasting delivered small-to-moderate additional benefits in weight loss, body composition, lipid levels, and systolic blood pressure — benefits not observed with other intermittent fasting approaches. METHODOLOGY: Weight loss reduces cardiometabolic risks and the burden of chronic disease. Intermittent fasting — alternating periods of eating and fasting — may be a more sustainable alternative to daily calorie restriction, but its benefits compared with those of continuous calorie restriction or ad libitum diets remain unclear. Researchers conducted a systematic review and network meta‐analysis of 99 randomized clinical trials to compare intermittent fasting regimens with continuous calorie restriction and ad libitum diets. Intermittent fasting regimens were time-restricted eating (16-hour fasting period followed by an 8-hour eating window), alternate-day fasting (24-hour fast on alternate days), and whole-day fasting (5 days of unrestricted eating and 2 days of fasting). The included trials, which ranged from 3 to 52 weeks, involved 6582 adults (median age, 45 years; median BMI, 31.3; 66% women), of whom 5862 had existing health conditions such as diabetes, metabolic syndrome, or metabolic dysfunction-associated fatty liver disease. The primary outcome was body weight, and secondary outcomes encompassed anthropometric measures, glucose metabolism markers, blood pressure, lipid profiles, liver function, and C-reactive protein levels. TAKEAWAY: A total of 54 studies evaluated ad libitum diets, 53 assessed continuous calorie restriction, 25 examined alternate-day fasting, 40 investigated time-restricted eating, and 38 focused on whole-day fasting. All intermittent fasting and continuous calorie restriction strategies reduced body weight compared with ad libitum diets, with alternate-day fasting showing additional benefit over continuous calorie restriction (mean difference, -1.29 kg; 95% CI, -1.99 to -0.59). Alternate-day fasting led to greater weight reduction than time-restricted eating (mean difference, -1.69 kg; 95% CI, -2.49 to -0.88) and whole-day fasting (mean difference, -1.05 kg; 95% CI, -1.90 to -0.19). The slightly greater weight loss benefits with alternate-day fasting were observed only in the 76 trials with less than 24 weeks of follow-up; however, the 17 moderate-to-long-term trials (≥ 24 weeks) demonstrated greater weight loss for all diet strategies, with no differences between intermittent fasting strategies. Alternate-day fasting was associated with greater reductions in BMI, non-high-density lipoprotein cholesterol levels, and triglyceride levels compared with time-restricted or whole-day fasting. IN PRACTICE: 'The value of this study is not in establishing a universally superior strategy but in positioning alternate-day fasting as an additional option within the therapeutic repertoire,' experts wrote in an accompanying editorial. 'Intermittent fasting does not aim to replace other dietary strategies but to integrate and complement them within a comprehensive, patient-centered nutritional care model,' they added. SOURCE: The study was led by Zhila Semnani-Azad, Department of Nutrition, Harvard T.H. Chan School of Public Health in Boston. It was published online on June 18, 2025, in BMJ . LIMITATIONS: While diet quality on nonfasting days may influence fasting outcomes on alternate days, this relationship has not yet been systematically evaluated in clinical trials. Considerable heterogeneity and incoherence in body weight outcomes across the diet strategy comparisons led to a downgrade in the certainty of the evidence. DISCLOSURES: This study was supported by the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes, the Canadian Institutes of Health Research, and other sources. Some authors received research support, honoraria, grants, speaker fees, served on advisory boards, and had several other ties with certain pharmaceutical companies and institutions.
News.com.au
3 days ago
- Business
- News.com.au
Health Check: Mayne Pharma shareholders back $600m ‘phantom' takeover offer
Mayne investors today strongly endorsed Cosette's non-existent takeover offer Audeara's improving sales are loud and clear We ferret around for all the latest clinical trial news Mayne Pharma (ASX:MYX) shareholders have overwhelmingly approved the company's $600 million takeover scheme of arrangement, even though suitor Cosette has terminated the deal. At the Melbourne meeting, the company reported 699 proxy votes in favour of 98.57%, compared with four 'nays' accounting for 0.95%. Open proxies accounted for a further 0.47% or so. The deal is a phantom one, in the sense that Cosette pulled out on the grounds that adverse material events had occurred. Such a withdrawal is allowable under the scheme implementation deed (SID). In a cross claim, Cosette alleges Mayne engaged in misleading or deceptive conduct. Mayne disputes these allegations and says the SID – now glowingly endorsed by investors – remains valid. The company has filed NSW Supreme Court proceedings to seek such a ruling. Chairman Frank Condella told holders the SID was subject to a favorable court adjudication, 'in the absence of any other agreement being able to be reached with Cosette in relation to the dispute.' He warned that if Mayne's legal quest fails, the company may be subject to 'financial detriment, including damages claims and/or costs orders and the payment of a break fee to Cosette ." That said, Mayne directors believe that it's in the shareholders' best interest to pursue litigation. Hear! Hear! Audeara in bullish trading update The maker of own-brand and white label devices to assist hearing, Audeara (ASX:AUA) says it is poised for a record year on the back of sales orders from two key clients. The company reported unaudited revenue for the year to June (eleven months) of $3.64 million, up 14% on the previous year and 25% higher than in the 2022-23 year. Audeara's fortunes have been underpinned by the launch of Taiwan hearing device leader Clinico's co-branded sound buds, which imbed Audeara's 'secret sauce' tech. This tie up resulted in an initial $570,000 order. The company also received a follow-up order of $917,000 from 400-year-old musical instrument maker Avedis Zildjian. Audeara also grew Australian wholesale sales by 16%, to $1.67 million. Management expects additional growth in coming weeks, including sales to wholesalers, retailers and resellers. We're 'earing different things about Cochlear Still on hearing devices, broking analysts have offered different takes on Cochlear's (ASX:COH) prospects after the company last Thursday downgraded full-year earnings expectations by 2-5%. And that's okay – it's a democracy after all. The company said its moderated outlook resulted from slowing growth for both cochlear implants and sound processors in its developed markets. Investors ponder to what degree Cochlear's new off-the-ear (OTE) Kanso 3 sound processor – and the next-gen implant Nucleus Nexa – will rev up sales. UBS has upped its call on the stock from neutral to a buy, with a new price target of $325 compared with $285 previously. The company believes Cochlear's new implants can boost its compound annual revenue growth by 10% over the next three year. Over this period, the firm expects Nucleus Nexa to increase Cochlear's global implant share by 3%, to 63%. Cochlear this month is launching the device in Europe and the Asia Pacific. Maintaining a 'hold', Morgans lowers its 'target price' from $286.24 to $281.36. 'While new systems tend to precede re-rates, we remain cautious,' the firm says. Morgans notes Nucleus Nexa 'appears more about refining the user experience as opposed to offering technological advancements as seen with prior implant iterations.' Sounds like the Iphone phenomenon, in that the 'wow factor' is dulled with every new release. Argenica pursues brain damage study Today's clinical trial updates come courtesy of rats, mice and ferrets and we thank these rodents and weasels for their sacrifice. In the case of Argenica Therapeutics (ASX:AGN), the brain and neurogenerative injuries specialist will forge head with a trial of its drug candidate ARG-007. This is for the hard-to-treat traumatic brain injury (TBI). This go-ahead follows a second preclinical study in a large cohort ferret. This showed ARG-007 resulted in 'significant long-lasting reduction in brain cell damage and inflammation following injury.' This 14-day study extended an initial three-day pilot effort. Aregenica says the ferret model 'closely resembles the gross anatomy of the human brain'. Combined with previous rat studies and the pilot ferret trial, this provides a 'robust preclinical data package'. TBI affects 69 million people globally annually, with no approved therapies. The University of Adelaide carried out the study, partly funded by a federal grant. The results should soothe investor disappointment over last week's setback, when the FDA placed a 'clinical hold' on Argenica's request to carry out a US ischaemic stroke trial. However, the company says its local phase II trial, now at dosing stage, is unaffected. Inoviq's (Exo) Ace trial news Inoviq (ASX:IIQ) reports that in vitro lab work has shown that one of its drug candidates killed 88% of aggressive triple negative breast cancer and lung cancer cells. The treatment deploys exosomes: tiny particles that deliver targeted therapies. The story gets complex because Inoviq uses engineered immune cell particles called CAR-NK-EVs, overlaid with its special process called Exo-Ace. The short explanation is the efforts could lead to an 'off the shelf' therapy that is faster, safer and more effective than traditional cell therapies (such as burgeoning CAR-T treatments that involve tricking up the T cells). Inoviq now will test the treatment in mice. It's very early days, but Inoviq shares this morning surged as much as 21%. Lumos enrolls its 500th patient Meanwhile, Lumos Diagnostics (ASX:LDX) has enrolled its 500 th patient in a study to clear its Febridx assay for US sale. A point-of-care test, Febridx rapidly distinguishes between bacterial and viral infections. The tricky bit is enrolling enough bacteria-positive patients and to date the company has corralled 78 of the requisite 120. By reaching 500 patients, Lumos has pocketed a US$298,457 milestone payment from its partner, the Biomedical Advanced Research and Development Authority (BARDA). BARDA hands over another US$746,143 when the trial enrols the last patients. Lumos doesn't specific a number, but expects the process to complete by the end of 2025. Lumos is seeking so-called CLIA (Clinical Laboratory Improvements Amendment) waiver. This enables simple tests to be used by less trained staff such as nurses and receptionists.
Medscape
3 days ago
- Health
- Medscape
Skills Lab: Understanding Misconceptions About PFS in Cancer Care
This transcript has been edited for clarity. Hello, everyone. This is Dr Bishal Gyawali, from Queens University, Kingston, Canada. I'm back again in this Skills Lab Series on Medscape. Thank you for joining us in the past few lectures. Today is going to be the last lecture regarding surrogate endpoints. We will discuss how physicians and patients understand surrogate endpoints. Do they clearly understand, and do they make the right clinical decisions based on their understanding of surrogate endpoints? First, let's talk about patient understanding of progression-free survival (PFS), the most commonly used endpoint in advanced cancer drug trials. In fact, colleagues from the FDA conducted a fantastic study, in which they asked participants about their understanding of surrogate endpoints, and how they did this was very clever. They showed a direct-to-consumer television advertisement about a cancer drug, and the advertisement mentioned that the drug improved progression-free survival. It did not mention anything about overall survival (OS) or anything else. It just said that the drug improved progression-free survival. There were almost 1000 participants in this study and, after watching that advertisement that mentioned improved progression-free survival, more than 90% of the participants thought that the drug improved survival. There was no mention of overall survival, but just by hearing that it improved progression-free survival, they assumed that the drug improved overall survival, which is quite telling. The researchers went one step further. They did a fantastic intervention. Now the participants saw the same advertisement again, but this time the advertisement specifically mentioned that the survival data were unknown. It improved progression-free survival, but we don't know whether it improves [overall] survival. Even after that disclosure, 40% of the participants continued to believe that the drug improved survival, and I think this is because we call it progression-free survival. When we call it that, they hear the last word, "survival," and they inherently assume that if a drug improves progression-free survival, it improves their survival. Even after disclosing that survival effects are unknown, 40% of the participants continued to believe that the drug improves survival. One more very interesting study was conducted in 100 patients with advanced cancer in Canada. These were actual patients who were receiving treatment for cancer. PFS and OS were explained to these patients, and they were given a hypothetical scenario about a drug that improved PFS and had some toxicities but did not improve OS. In this experiment, 17% of the patients said they would prefer to receive the drug even if there was no PFS benefit. This is similar to what we see. Some of our patients just want something. They just want a drug. Even if there is no PFS or OS benefit, they just do not want to give up. Of the patients, 26% said they would want the drug for some PFS benefit, within the range of 3-9 months. If the drug improved PFS between 3 and 9 months, even if it did not improve OS, patients would still want to get the drug. However, the majority of them, 51%, would decline the drug, regardless of PFS benefit. This is important. What this is telling us is that if the drug does not offer any OS advantage, more than half of our patients would decline a drug with toxicities, irrespective of how big the magnitude of the PFS benefit is. Therefore, we wrote a paper in The Lancet Oncology back in 2022, in which we called on the community to change the name of progression-free survival because it is confusing, and patients assume it is a survival advantage when it's actually not. If a drug does not improve survival, then they would probably not want a drug with PFS benefit alone. We said that it's time for a new name, and we proposed that instead of PFS, progression-free survival, we should call it PFI — progression-free interval — because it gets rid of the word "survival" and patients won't be confused. Now, let's talk about physicians' understanding of surrogate endpoints. Do physicians understand this well? This is a very recent paper that we published in ESMO Open . This was a mixed-methods study of oncologists' perceptions on endpoints, benefit, price, and value of cancer drugs. We conducted this study among oncologists in India, so there might be some limitations about how applicable it is elsewhere, but I don't think the results we found are very different from what we would find in any other country. First, we found that 20% of oncologists rarely use cancer drugs that improve only response rate but not survival. Almost an equal percentage said that they would often use drugs that improved response rate but not survival. In regard to PFS, 20% of oncologists rarely used cancer drugs that did not improve survival and only improved PFS, but 48% of them often used such a drug. We asked them the reasons for this. First, let's talk about response rate. Among the oncologists who said they would not use a drug that improves only response rate, the most common reason was lack of any effect on survival or quality of life because the drug just shrinks the tumor. It does not help patients live longer or better, so what's the point? The second was toxicity, and the drug will definitely have many side effects. That was the reason why they did not want to use a drug with response alone. Among oncologists who said they would use the drug based on response rate alone, when we asked why, the most common answer was for symptom relief or improved quality of life. This is quite interesting because there are no data to say that response rate leads to improved quality of life or symptom relief. If it is in a tricky location, then it can, but there is no evidence that, in general, shrinking a tumor leads to improved quality of life. This indicates that oncologists' understanding of surrogate endpoints is also not optimal. The second most common reason was to downstage disease, which is understandable. The third one is also very interesting because they said "something is better than nothing." That means they know that response rate does not lead to improved clinical outcomes, but they can't just do nothing for their patients. They have to do something and the patient wants something, so something is better than nothing. The fourth one is very interesting. They talk about the impact of drug approval and having it included in guidelines. Even if they know that it's based on response rate alone and they don't want to use the drug, if it's approved and if it's in the guidelines, then they feel like they're forced to use it. Some of the oncologists also said that it's on a case-by-case basis. For example, if they have a drug that is cheaper or a biosimilar for a drug that improves response rate alone, they would use it. For rare cancers or where there is no other option, as we discussed, they would use such a drug. The most common reason for not using a drug based on PFS alone was the lack of effect on survival because it was not known whether the drug improved survival or not, which is very appropriate. Reasons in support of PFS were very interesting. The number-one reason here was cost. Oncologists said that a drug that improves PFS costs less than a drug that improves OS. The patients cannot afford the expensive drug, so they're using a cheaper drug. Again, this is very interesting because that's not true, especially in the context of the United States, Canada, and other high-income countries where we have done these studies. There is no correlation between whether the drug is approved based on PFS or OS and the price of the drug. A drug approved based on PFS can cost even more than a drug that is approved based on OS. The second reason was the impact of medical literature. If, in the editorials, commentaries, and CMEs, people are promoting a drug that is based on PFS alone, then that leads to their use. Then, on a case-by-case basis, people also talk about cost-effectiveness and for rare cancers or lack of alternatives. Overall, I'm trying to show that when oncologists understand that it's only response rate or PFS, they still use these drugs based on some misguided assumptions that delaying PFS or improving response rate leads to improved quality of life, which is objectively untrue, and that drugs approved based on surrogate endpoints cost less than drugs approved based on OS, which is also untrue. It's also interesting that we have this culture of always trying to do something rather than having that difficult discussion about end of life. Doing something is always easier than doing nothing, so we end up prescribing these drugs, although we know that it does not benefit patients. I think these findings are quite interesting, and I want our entire oncology community to be aware of these biases within ourselves. To close the loop, we also asked these oncologists about whether magnitude and price matter. They said that, for a drug that impacts only PFS, they would want to see at least a 4.5-month improvement in PFS, with the range of answers from 1.5 to 12 months, so quite a big range there. The price is interesting. This is not applicable to high-income countries. This is applicable only in the Indian context. They said that 120 USD per month was appropriate for such a drug. For OS, again, they wanted an improvement of 4.5 months, with a range of 2-24 months. They said 360 USD per month was justified. It's not about the exact number, but what they are telling us here is that a drug that improves OS can cost up to three times more than a drug that improves PFS alone. If you think about it the other way around, a drug that only improves PFS but not OS should be costing one third of the drugs that improve OS. That's not the case in reality. We talked about all the surrogate endpoints in these lectures and today is the end of this topic. To clarify, just because a trial's endpoint is overall survival does not necessarily mean that the benefits are meaningful. There can be several other issues, which we'll discuss in our subsequent lectures. The next few lectures will talk about statistical analysis, sample sizes, power calculations, and so on. Stay tuned. Thank you.
Medscape
3 days ago
- Health
- Medscape
New Guidelines to Make Psychedelic Trials Safer, FDA-Ready
An international expert panel has developed the first consensus-based framework for reporting 'set and setting' variables in psychedelic clinical trials. The guidelines create a standardized protocol for psychedelic clinical trials that accounts for the mental state of the user and the environment in which the psychedelic experience takes place. The Reporting of Setting in Psychedelic Clinical Trials (ReSPCT) guidelines were developed using the Delphi method and involved 89 experts in the field from 17 different countries. The expert panel included not only clinicians and researchers but also past clinical trial participants who provided the all-important lived experience. They were published online on June 3 in Nature Medicine . Context Matters It's common knowledge that 'set and setting' — the mindset of a person taking a psychedelic and the environment in which they take it — have a 'huge impact on the psychedelic experience itself,' co-lead author Chloé Pronovost-Morgan, MD, psychiatry resident, McGill University, Montreal, Quebec, Canada, told Medscape Medical News . 'The same drug at the same dose can produce diametrically opposing reactions depending on context — ranging from terrible anxiety to mystical-like experiences,' she added. Yet, a recent systematic review showed that most psychedelic trials provide minimal detail about context, making it difficult to understand what actually took place and what participants experienced. 'Were they given psilocybin in a cozy room in the countryside overlooking a field or in a sterile hospital while in a giant brain scanner? If we know that context matters, then we need to know what the context actually was. Otherwise, study findings are difficult to interpret, replicate, and apply,' said Pronovost-Morgan. The ReSPCT framework consists of 30 variables divided into four sections the panel deemed essential to report. The first focuses on the physical and sensory environment. This includes details about the study setting (eg, indoors or outdoors, private clinic, hospital, or retreat center), room design (whether a specific ambiance was intentionally created — such as nature-inspired, psychedelic-themed, ceremonial/shamanic, or home-like), sensory modulation tools (such as the use of eye shades or noise-cancelling headphones), and the presence of objects or decorations (including artwork, candles, statues, or religious and spiritual items). 'Context is often not appropriately reported, including studies I've participated where I wasn't the principal investigator' Matthew W. Johnson, PhD, with the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, told Medscape Medical News . Johnson, who wasn't part of the panel, said he's had to 'battle to get in important methods into papers such as the presence of religious iconography.' Religious or spiritual items in the room may lead participants to interpret their experiences in a more spiritual way. Johnson noted that some researchers hesitate to report these details out of concern that a spiritually charged setting could cast doubt on the results — implying the experience was influenced rather than spontaneous. Need for Realistic Information The second section of the guidelines outlines key aspects of the dosing session procedure that should be reported. This includes who was present during the session; whether music or a soundscape was used; the verbal and physical interactions that took place and how consent was obtained; the level of participant autonomy and control over activities and the environment; details of the dosing regimen — including dosage, frequency, route of administration, and duration of the session; and any disturbances or interruptions that may have affected the quality of the experience. The third section focuses on the therapeutic framework and protocol. This includes reporting specific topics covered and activities conducted during preparation sessions — such as reviewing the patient's medical and psychological history, setting intentions and expectations, addressing questions or concerns, and providing psychoeducation. It also calls for documentation of the credentials and training of the staff involved, including aspects of cultural competence and safety. Johnson noted the amount of preparation time is often not explicitly reported in trial publications. 'We need realistic information — was it 8 or 12 hours of preparation — not the shorter figures often listed. There is often more time spent with participants than is reported, in my experience,' he said. The fourth and last section of the guidelines addresses participants' subjective experience, capturing their perceptions of the environment — including therapeutic rapport, sense of comfort, and feelings of safety. Pronovost-Morgan said a broader goal of the guidelines is not only to document the objective aspects of the environment but also to capture participants' subjective experiences, such as whether they felt physically safe during the session. She explained that the guidelines are primarily intended to improve the consistency and clarity of reporting in psychedelic trials while also encouraging research teams to take a more deliberate and thoughtful approach to designing studies. Paving the Way for Evidence-Based Care The panel encourages researchers to incorporate the 30 ReSPCT items in either the main text or supplementary materials of their publications. Over time, this practice could allow for comparison of outcomes across trials based on these contextual variables, helping to identify which factors have the greatest influence on clinical results. 'That kind of clarity could help us move beyond tradition or intuition and toward evidence-based contextual care. The field already has a sense that certain variables — like music or the therapeutic team — matter enormously. But I suspect some of the less obvious items on the list will turn out to be surprisingly influential, which is exciting to think about,' said Pronovost-Morgan. Until now, a key limitation of psychedelic clinical trials has been the insufficient consideration of how a participant's mindset and environment can influence the effects of substances like 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin. This lack of standards has already had consequences beyond the research lab. As previously reported by Medscape Medical News , the FDA recently rejected MDMA-assisted therapy for posttraumatic stress disorder (PTSD), citing inconsistent reporting across trials as a key reason for its decision. Paul E. Holtzheimer, MD, director of the VA's National Posttraumatic Stress Disorder Brain Bank and member of the FDA panel that rejected MDMA for PTSD, said the therapy element is 'a bit of a black box,' adding that 'it's a relatively vague, ill-defined treatment.' 'We think the ReSPCT guidelines will help researchers, clinicians, and regulatory bodies gain a better understanding of what lies in that 'box,' so that we can understand what these therapies entail as a whole — including the nondrug variables that are crucial to safety and efficacy,' said Pronovost-Morgan. 'Our guidelines will also help in replicating results and understanding the true therapeutic potential of psychedelics,' co-senior author Leor Roseman, PhD, Department of Psychology, University of Exeter, Exeter, England, added in a statement. That should increase the chances of regulatory approval for psychedelics, the panel predicted. Co-senior author Kyle Greenway, MD, MSc, from McGill University's Department of Psychiatry, emphasized that the importance of carefully considering context extends beyond just psychedelic drugs. 'Converging lines of preclinical and clinical evidence support that contextual influences can be significant for consciousness-altering effects for a wide variety of drugs, from antidepressants and benzodiazepines to alcohol and opiates. Psychedelic drugs may provide the most striking examples of drug-context interaction effects, but contextual influences warrant greater scientific and clinical attention for psychoactive substances much more generally,' said Greenway.
