Drugs Established for Other Health Conditions May Provide Cancer Benefit

CURE, CURE Spring 2022,

Drugs that control blood pressure and lower cholesterol, among others, may help patients derive greater benefit from cancer treatment, but study findings have left researchers reassessing their next moves.

Several existing drugs, including those that treat high blood pressure and high blood sugar levels, are being investigated alongside other treatments in patients with cancer to see if they provide a survival benefit, although more research is needed to determine whether this is a possibility.

There may be some overlap on what cardiometabolic drugs — those that focus on dysfunctions related to heart disease, diabetes and chronic renal failure — treat and certain aspects of cancer. For example, drugs that control blood pressure, such as angiotensin-converting enzyme (ACE) inhibitors, may alter a patient’s vasculature, which may lead to improved therapy responses. In addition, some common risk factors in breast cancer can also increase one’s risk for heart disease, such as higher insulin levels and higher inflammation.

As it stands, some experts would frown upon using these cardiometabolic drugs for potential cancer survival benefit.

“I would not recommend metformin or aspirin for the purpose of treating breast cancer based on large trials that have tested the impact of these drugs on cancer recurrence and survival in women,” said Dr. Jennifer A. Ligibel, director of the Leonard P. Zakim Center for Integrative Therapies and Healthy Living at Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School in Boston, in an interview with CURE ®.

Despite this recent bump in the road in researching cardiometabolic drugs in patients with cancer, other experts remain hopeful.

“It’s safe to say that (cardiometabolic drugs have) the potential to benefit all cancer types and stages, but in the clinical setting, each of those tumor types and stages of disease are going to have to be investigated to determine if this potential can be realized,” Dr. Zachary Morris, an associate professor and vice chair of the Department of Human Oncology at the University of Wisconsin School of Medicine and Public Health in Madison, told CURE®.

“It will take some time to understand whether and how best to take these agents in conjunction with other cancer therapies. They may work for some diseases or together with certain other treatments better than others, but this remains to be determined through clinical research.”

POTENTIAL BENEFITS IN CERTAIN CANCER TYPES

Morris and his colleagues have conducted research in this space and their findings include those of a study published in Cancer in 2016. The authors assessed the increased tumor response to neoadjuvant radiation in patients with rectal cancer who took ACE inhibitors or angiotensin receptor blockers, both of which have been traditionally used to lower blood pressure in patients with hypertension. Findings from this particular study demonstrated that incidental use of those two drugs that lower blood pressure was correlated with a three-fold increase in the rate of complete response (the disappearance of all signs of cancer as a response to treatment).

“Some of our drugs that might impact vasculature or blood pressure, for example, could have effects on blood perfusion of the tumor microenvironment,” Morris said. “It’s not that the drugs themselves directly kill cancer cells, but they may help us to deliver other things like chemotherapy that could then better kill that tumor, or, in the case of radiation, we need oxygen in the tumor to most effectively kill tumor cells with radiation. Just by improving the blood flow to a tumor during the time when radiation is being given, it may impact the efficacy of radiation in that local environment.”

Other studies have been conducted including one whose results were published in Cancer Medicine in 2021. Findings from this study demonstrated that blood pressure medications may improve survival in patients with colorectal cancer.

A number of older studies suggested that metformin in particular might help to prevent breast cancer, and that women who took metformin after a cancer diagnosis might have a lower risk of dying from breast cancer. These studies led to the development of a large trial called MA-32 that tested whether adding metformin as a part of breast cancer treatment would reduce the risk that the cancer returned after initial treatment.

Early results from the MA-32 trial, which included more than 3,000 women, showed that patients who received metformin during treatment had improvements in weight and metabolic factors compared with those who received placebo. However, the final results of the study published early this year showed that metformin did not prevent or stop the spread of breast cancer.

“That was very disappointing,” Ligibel said. “We were certainly hoping that metformin would be a helpful treatment for breast cancer, but this study unfortunately showed that metformin was not helpful as a breast cancer treatment. This is why it is so important to conduct clinical trials. Sometimes, treatments are not helpful even when there’s great preliminary information that says maybe this (medication) makes a difference.”

TIME TO REGROUP

Based on the negative results of recent studies in this area, Ligibel said, “We’re in a regrouping phase for this concept.” She added that the benefit observed in earlier studies of metformin may be due to the types of studies that had previously been conducted.

For example, some have been observational in nature, meaning that researchers asked a large group of patients with cancer about the medications they are taking. Although researchers are able to observe any patterns, the study doesn’t take into consideration whether other factors play an effect, such as why patients are taking a particular drug or what other health conditions they might have.

In addition, preliminary studies are often done in animal models, and although these models can be helpful in the trajectory of research, dosages can be different in animals compared with humans.

More research is needed to deter- mine whether cardiometabolic drugs may have benefits in other kinds of cancer, despite the disappointing findings in breast cancer. Some areas of interest include which cancer types may benefit from this regimen compared with others; whether patients obtain the benefit immediately or whether the drug must be taken for a certain amount of time before initiating cancer treatment; and whether statins (which lower cholesterol) and aspirin (often used to prevent blood clots) pose a similar benefit in patients with cancer.

Morris mentioned that patients can play a huge role in the studies needed in this area.

“We really appreciate and respect the patients when they contribute to clinical trials,” Morris said. “It’s such an altruistic gesture because we don’t know if (a trial is) going to benefit a given patient, but we know that it will benefit our understanding of cancer and the disease overall. ... If patients are interested ... (and) if it seems like the right thing for them, ... participating in clinical trials is a really thoughtful gesture on (their) behalf.”

Ligibel also advised patients to take good care of themselves with physical activity, a healthy diet and maintaining a healthy weight.

“So far, the medications haven’t really shown as much benefit, but there’s a huge benefit in living a healthy lifestyle,” she said, “(and,) if you do have diabetes or high blood pressure, in making sure that you take care of those conditions. ... It is incredibly important if you have cancer or you don’t have cancer to make sure that your blood pressure is under good control, that your diabetes is under good control. We know that managing those conditions absolutely prolongs life and is very important to people’s overall health.”

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.