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Xtandi drug combo cuts risk of death by 58% in prostate cancer patients

A new drug combo has been shown to boost metastasis-free survival by 58% in prostate cancer patients at high risk of biochemical recurrence.
Astellas Pharma and Pfizer say the drug Xtandi combined with an androgen deprivation therapy has the potential to be the new standard of care in patients with high risk biochemical recurrence (BCR) if a label expansion is approved.
The two companies have reported full data at the American Urological Association Annual Meeting from a late stage phase 3 trial, dubbed Embark.
In the trial Astellas and Pfizer tested out Xtandi plus leuprolide against a placebo plus leuprolide in 1,068 men with non-metastatic hormone-sensitive prostate cancer with a high-risk of BCR.
The Xtandi-leuprolide blend reduced the risk of metastasis or death by 58% versus the placebo plus leuprolide in the multi-national trial conducted at sites in the United States, Canada, Europe, South America and the Asia- Pacific region.
The trial evaluated patients in three study groups – Xtandi plus leuprolide, placebo plus leuprolide, and Xtandi monotherapy – in men with non-metastatic hormone-sensitive prostate cancer with high-risk BCR.
The main aim of Embark was to assess metastasis-free survival (MFS).
Astellas and Pfizer reported that secondary endpoints saw improvements.
In the Xtandi monotherapy group, the drug reduced the risk of metastasis or death by 37%, compared to leuprolide plus placebo.
The combo arm of the trial reduced the risk of prostate-specific antigen progression (PSA-P) by 93% while the monotherapy lowered it by 67%.
The progression risk in starting a new antineoplastic therapy was reduced by 64% in those on Xtandi plus leuprolide and 46% in those on Xtandi monotherapy, versus the leuprolide placebo combo.
The most common adverse effects in the combo arm of the study were fatigue, hot flush and arthralgia (painful or stiff joints). In the patients on the Xtandi monotherapy, the most frequent unfavourable reactions were fatigue, gynecomastia (an overdevelopment or enlargement of the breast tissue in men), and arthralgia.
Detailed results from the trial will now be submitted for peer-reviewed publication. Additionally, the Embark data will be discussed with regulatory authorities, including the US Food and Drug Administration (FDA), to expand the use of Xtandi into a fourth cancer indication.
Xtandi – which is also known as enzalutamide – has been approved for use as a daily therapy in the United States since 2019 in men with metastatic hormone-sensitive prostate cancer, metastatic castration-resistant prostate cancer and non-metastatic castration-resistant prostate cancer.
It was approved for use by the European Commission in May 2021.
Leuprolide – also known as Eligard and Lupron – is an already-approved drug commonly used to treat symptoms of advanced prostate cancer. It works by lowering testosterone levels, which can help slow the growth of cancer cells.
In a statement, Neal Shore, primary investigator for Embark and US chief medical officer of Urology and Surgical Oncology, said the study showed that the drug combo was “statistically significant” for high-risk BCR patients.
He said: “There are patients with localized prostate cancer who undergo prostatectomy or radiation therapy in an attempt to cure their disease, but, unfortunately, some patients will develop BCR.
“Importantly, some patients with BCR are at very high risk for developing metastatic disease, which can lead to a cascade of therapeutic interventions. The clinical goal of BCR therapy is to delay cancer progression and avoid metastatic disease.
“The MFS results from the Embark study demonstrate that this intervention with Xtandi plus leuprolide was statistically significant for patients with high-risk BCR.”
Stephen Freedland, director for the Center for Integrated Research in Cancer and Lifestyle and co=principal investigator of the clinical trial, added: “The Embark study is a Phase 3 trial exploring the potential of enzalutamide in patients with non-metastatic hormone-sensitive prostate cancer with high-risk BCR.
“If approved, we hope to bring a new option to men earlier in the course of their disease.”
Prostate cancer is the second most diagnosed in men globally and the fifth leading cause of death. An estimated 1.4 million new cases of the disease and more than 375,000 deaths are reported every year.
The countries with the highest prostate cancer rates according to statistics compiled by the World Cancer Research Fund International are French Guadeloupe, French Martinique, Ireland, Barbados and Saint Lucia.
There is strong evidence that being overweight and obese and being tall increase the risk of developing prostate cancer. Research suggests that diets high in calcium and high consumption of dairy products might also increase the risk.
Current treatment depends on how big the cancer is, if it has spread, and general health. But the most common are surgery, chemotherapy, radiotherapy and hormone – or androgen suppression – therapy.
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AI can predict Alzheimer’s with almost 93% accuracy, researchers say

Alzheimer’s AI can predict the disease with nearly 93 per cent accuracy using more than 800 brain scans, researchers say.
The system identified anatomical changes in the brain linked to the onset of the most common form of dementia, a condition that gradually damages memory and thinking.
The findings build on years of research suggesting AI could help spot early Alzheimer’s risk, predict disease and identify patients whose condition has not yet been diagnosed.
Benjamin Nephew, an assistant research professor at the Worcester Polytechnic Institute in Massachusetts, said: “Early diagnosis of Alzheimer’s disease can be difficult because symptoms can be mistaken for normal ageing.
“We found that machine-learning technologies, however, can analyse large amounts of data from scans to identify subtle changes and accurately predict Alzheimer’s disease and related cognitive states.”
The study used MRI scans, a type of detailed brain imaging, from 344 people aged 69 to 84.
The dataset included 281 scans showing normal mental function, 332 with mild cognitive impairment, an early stage of memory and thinking decline, and 202 with Alzheimer’s.
The scans covered 95 of the brain’s nearly 200 distinct regions and used an AI algorithm to predict patients’ health.
Being able to use AI to help diagnose Alzheimer’s earlier could give patients and doctors crucial time to prepare and potentially slow the progression of the disease.
The analysis showed that one of the top predictive factors was brain volume loss, or shrinkage, in the hippocampus, which helps form memories, the amygdala, which processes fear, and the entorhinal cortex, which helps provide a sense of time.
This pattern held across age and sex, with both men and women aged 69 to 76 showing volume loss in the right part of the hippocampus, suggesting it may be an important area for early diagnosis, the researchers noted.
However, the research also found that the way brain regions shrink differs by sex.
In females, volume loss occurred in the brain’s left middle temporal cortex, which is involved in language and visual perception. In males, it was mainly seen in the right entorhinal cortex
The researchers believe this could be linked to changes in sex hormones, including the loss of oestrogen in women and testosterone in men.
These conclusions could help improve methods of diagnosis and treatment going forward, Nephew said.
More than 7.2m Americans are living with Alzheimer’s, according to the Alzheimer’s Association.
More research is being done to reveal other impacting factors.
Nephew said: “The critical challenge in this research is to build a generalisable machine-learning model that captures the difference between healthy brains and brains from people with mild cognitive impairment or Alzheimer’s disease.”
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