Metformin/statin combo therapy reduces PCa mortality

Treatment with metformin plus a statin or with a statin alone significantly reduces overall and disease-specific mortality in men with high-risk prostate cancer, according to the findings of a population-based study presented at the American Society of Clinical Oncology annual meeting in Chicago.  

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Using Surveillance, Epidemiology, and End Results-Medicare linked data, the study identified almost 21,000 men diagnosed with high-risk prostate cancer between 2007 and 2009. Based on follow-up through Dec. 31, 2011, hazard ratios for mortality outcomes associated with use of metformin and/or a statin were calculated in a Cox regression analysis adjusting for numerous sociodemographic, clinical, and prostate cancer-related variables.

Compared to the reference group of men on neither agent, men on a statin plus metformin had significant reductions in both overall mortality (34%) and prostate cancer-specific mortality (PCSM; 43%). Use of a statin alone was associated with slightly lower reductions in overall mortality (25%) and PCSM (40%), but the benefits were still statistically significant.

Findings from a sensitivity analysis focusing on patients with a comorbidity score of 0 or 1 showed similar significant reductions in overall mortality and PCSM among men using the combination regimen or a statin alone. Use of metformin alone, however, had no significant benefit in reducing overall mortality or PCSM in the overall population or in the subgroup with minimal comorbidities, reported first author Grace L. Lu-Yao, PhD, of Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick. 

NEXT: Findings consistent with preclinical results

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“There is evidence from a recently published pre-clinical study showing the combination of metformin and a statin is more effective than docetaxel [Taxotere] for reducing prostate cancer progression,” Dr. Lu-Yao told Urology Times.

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Dr. Lu-Yao“To our knowledge, this is the largest clinical study to assess the potential effect of combination metformin-statin therapy on PCSM, and the findings are consistent with the preclinical study results. However, a lot more work has to be done before a large-scale intervention trial can be undertaken to investigate the potential efficacy and safety of dual treatment with metformin and a statin.”

Dr. Lu-Yao explained that while the study was able to control for multiple confounders that would affect survival, it would have been desirable to include information on body mass index, cholesterol levels, and the timing and duration of statin therapy.

“We extracted data on medication use from Medicare Part D, but complete information is only available since 2007. Therefore, we could not look back to determine if statin use preceded the prostate cancer diagnosis and for how long. That is important considering existing evidence showing that a benefit of statin use for improving prostate cancer outcomes is greater among men who were already on a statin at the time of their diagnosis compared to those who started a statin after,” she said.

“In addition, it would be useful to have information on cholesterol levels so that we could investigate whether men who benefit most from being on a statin are those with high cholesterol.”

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Potency of statin treatment may also be an important factor influencing its effect on PCSM, and Dr. Lu-Yao and colleagues hope to get funding that will allow them to probe the database further in order to investigate that issue.

NEXT: Short duration of follow-up a limitation

She acknowledged that short duration of follow-up is another limitation of the study.

“We restricted our analysis to men with high-risk prostate cancer to improve our ability to detect a difference in PCSM, if it existed. Nevertheless, 3 years of follow-up is still extremely short for investigating that endpoint,” Dr. Lu-Yao said.

She also pointed out that while it was a negative finding, the lack of benefit of metformin alone for improving PCSM is important information considering current interest in mounting a large clinical trial to investigate metformin in men with prostate cancer.

Dr. Lu-Yao is an employee of and serves in a leadership capacity with Sun Pharma, and has stock and other ownership interests in and serves as a consultant/adviser to Merck Co., Inc. One of her co-authors has received institutional research funding from Novartis.

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