No clear evidence that adding diabetes drug to standard prostate cancer treatment reduces risk of death, but side effects of hormone therapy lessened
16 Sep 2024
Taking metformin (a drug commonly used for type 2 diabetes) alongside standard-of-care treatment did not significantly improve survival for people with metastatic prostate cancer, meaning it has spread beyond the prostate. This is according to new insights from the STAMPEDE clinical trial, run by the MRC Clinical Trials Unit at UCL.
Metformin did however lessen some of the common side-effects of standard hormone therapy, including weight gain, high cholesterol and high blood sugar. This may help reduce the risk of long-term health problems in the future.
These results were presented today at the European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain.
Prostate cancer is the second most common cancer in the UK and the most common cancer in men. Between, 2017 and 2019, 12,000 people died from prostate cancer. Of those who were diagnosed with prostate cancer between 2020-21, 19% were found to have metastatic disease.
Metastatic prostate cancer is usually treated with long-term hormone therapy to stop the disease from growing. For many people, this will control the cancer for many years. But, sometimes hormone therapy can stop working, and the disease returns.
Standard hormone therapy also affects the body’s metabolism, leading to side-effects, such as weight gain and insulin resistance. This may lead to diabetes and an increased risk of heart disease, stroke and other health problems in the future.
Metformin affects the way the body processes energy from sugars and fats. As cancer cells process energy differently to normal cells, researchers were interested in whether metformin could help prevent prostate cancer growth and progression. Researchers also aimed to see if metformin could prevent some of the side-effects of hormone therapy.
Between 2016 and 2023, 1,874 people with metastatic prostate cancer joined the metformin comparison of the STAMPEDE trial. Only people who did not have diabetes could take part in this comparison.
Researchers randomly assigned the participants to two groups: 938 people received the current standard-of-care treatment, while 936 people received standard-of-care treatment plus metformin.
The current standard-of-care for prostate cancer that has spread includes hormone therapy. Most patients also receive chemotherapy using the drug docetaxel as part of their standard treatment, and some patients receive radiotherapy.
The STAMPEDE team followed trial participants for an average of five years. On average, people taking metformin had a 10% lower risk of dying and lived for around six months longer than those who had standard treatment only. However, these differences between groups were not statistically significant. This means researchers cannot be sure that the observed difference was not due to chance.
Similar analyses looking how long people lived without their disease getting worse suggested that metformin might slow the growth and spread of the cancer. But, again, this difference was not statistically significant.
There was evidence to suggest that metformin may be more beneficial for prolonging survival and preventing the cancer from worsening in people whose cancer had spread more at the time of diagnosis, compared to those whose cancer had not spread as much. However, this is a preliminary finding, and researchers say further research is required to confirm and understand it.
Metformin did reduce some of the side-effects of hormone therapy. After two years, participants assigned metformin added to standard treatment had gained less than half as much weight (2kg) as those assigned standard treatment only (4.4kg). They also had lower levels of cholesterol and blood sugar. Furthermore, fewer patients in the metformin group reported signs of metabolic syndrome – a group of health problems which increase the risk of developing type 2 diabetes and heart disease.
While these results did not provide clear evidence that metformin can significantly improve metastatic prostate cancer survival, the findings suggest that it could help lessen some side-effects of hormone therapy. This could potentially reduce the risk of future health problems. Doctors and patients can use these results to help decide whether metformin might be right for them.
The data has not yet been published, nor analysed in full. Researchers are currently working on a paper which will be peer-reviewed and published in a scientific journal. Further research will focus on determining which patients benefit most from metformin.
Metformin is an inexpensive and safe drug, but the current drug license does not cover prostate cancer. This means it may not be immediately available within the NHS for use in people with prostate cancer.
The STAMPEDE trial first began in 2005 and the metformin comparison opened in 2016. STAMPEDE finished recruiting nearly 12,000 participants across all comparisons in 2023. It took place across more than 100 hospitals in the UK and Switzerland. The study was funded by Cancer Research UK and the Medical Research Council, with further support from Prostate Cancer UK and pharmaceutical industry collaborators including Janssen, Astellas, Clovis Oncology, Novartis, Pfizer, and Sanofi-Aventis.
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