Evidence Moves OTC Prevention of mCRC Closer to Reality

Andrew T. Chan, MD, MPH

As part of our coverage of the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting held May 29 to June 2 in Chicago, we are speaking with Andrew T. Chan, MD, MPH, program director for the gastroenterology training program at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School. At this year’s meeting, Dr. Chan will be discussing research presented on over-the-counter therapies for colon cancer.

  -Interviewed by Leah Lawrence 

Cancer Network: This year you will be discussing two abstracts dealing with secondary prevention in patients with colorectal cancer. Provide us with some background. Generally speaking, why are over-the-counter therapies appealing for secondary prevention in these patients?

Dr. Chan: I think we all have had the experience of meeting with patients diagnosed with colorectal cancer and having discussions about what they can do in terms of modifying their lifestyle to prevent a recurrence. It is foremost on patients’ minds, so it definitely represents an area that really requires more study.

We would like to be able to counsel our patients, as much as we can, about modifying their lifestyle in such a way that potentially could be an influence on their ultimate likelihood of developing recurrence of colon cancer. It is important to study this area and come up with some evidence to really support some potential recommendations.

Cancer Network: The first abstract you are going to discuss at the meeting, number 3503, looks at the use of vitamin D in the survival of metastatic colorectal cancer patients. Tell us a bit about this paper and why you think it is an important one for attendees to pay attention to this year.

Dr. Chan: For many years now there has been mounting evidence that vitamin D seems to play a role in the development of colorectal cancer and, potentially, the survival among patients with established colon cancer. There have been a series of very interesting epidemiologic studies that have shown that individuals who have lower levels of vitamin D or have lower overall vitamin D status seem to have a high risk of colon cancer, and there have also been some interesting studies that have shown that patients who have low levels of vitamin D also seem to do worse once they have been diagnosed with colorectal cancer.

It has been interesting because this has also been accompanied by data from the laboratory that have shown that vitamin D may actually have a mechanistic role in either the development of colorectal cancer or the progression of colorectal cancer. There seems to be some biological plausibility to the idea that vitamin D may be an important factor in determining cancer risk or the risk of developing recurrence once [patients] have been diagnosed.

This study is very interesting in that it really leveraged data from a randomized phase III clinical trial of chemotherapy plus bevacizumab or cetuximab in patients with metastatic colorectal cancer, and although the primary results of study did not show any significant difference in the intervention, it did provide an important opportunity to look at other factors that might be influential on survival. Many of the patients in the study also provided some baseline blood samples and this was something that could be used to actually determine associations between basic serum factors in relationship to survival.

In this study, the investigators actually measured plasma vitamin D in the serum samples that were taken at the beginning of the study and determined whether those levels of vitamin D had any association with survival over the course of the study. What they found is that individuals who had higher concentrations of plasma vitamin D did actually show significantly improved survival in the setting of metastatic colorectal cancer, irrespective of their treatment with chemotherapy. This was consistent with prior studies but was really noticeable because this was conducted within the context of a very rigorously done trial where patients were very closely followed for recurrence. Also, there was a lot of data available for the investigators to look at with respect to potential confounders or other aspects of biology that could have influenced the results.

It is very convincing evidence that potentially vitamin D may play a role in survival among patients who have established colon cancer and I think does form the basis for additional study in this area. We will need to also look at the possibility that clinical trials that are being done currently to treat patients with vitamin D might be influential on survival outcomes in the future, and, if so, I think this could represent an important adjunct to treatment for patients with colorectal cancer.

Cancer Network: The second abstract you will discuss, number 3504, moves away from vitamins and looks instead at the use of aspirin. What is known to date about the use of aspirin as it relates to colorectal cancer?

Dr. Chan: This is another interesting study, again looking at another over-the-counter agent, mainly aspirin.

Like vitamin D there are considerable data to support the association of aspirin with lower incidence of colorectal cancer over time. There are data from numerous epidemiologic studies done across many different patient populations and there has also been some very interesting data from randomized clinical trials, which have shown that patients who are randomized to aspirin therapy have a lower incidence of developing colorectal cancer over time. The link between aspirin and lower colon cancer risk is really quite convincing.

In tandem, there have also been a series of studies that have really shown that patients who are diagnosed with colorectal cancer, if they actually take aspirin after diagnosis, seem to do better from a survival standpoint. Patients who take aspirin after colon cancer diagnosis have been shown to have a 30%, 40%, sometimes even 50% improvement in overall survival, and sometimes that survival also may be differential according to molecular subtypes of colon cancer. There are some very interesting data to support the effect of aspirin after diagnosis.

The study presented at the meeting this year extends that data in the context of a cohort of about 25,000 patients with colon cancer in Norway. What makes this study very interesting is that these were patients who were diagnosed with colorectal cancer and were linked to a prescription database in which there was information on whether they took aspirin or not after diagnosis.

Among this very large population of patients they found that those individuals who were taking aspirin or were exposed to aspirin after diagnosis had a very substantial improvement in survival, up to 30% to 40%, which I think corroborates the findings of other studies and extends it to a very large number of patients in a population setting. This really adds to the evidence base that as a potential adjunct to other therapies, aspirin could play a role in our patients.

As with vitamin D, there are currently studies underway now to examine aspirin in the adjuvant setting in the context of randomized clinical trials. Hopefully those trials will also be supportive of this as a potential intervention. It will take several years for those studies to be completed, but I think, ultimately, that is the type of gold standard evidence that will hopefully move this therapy into the clinic so that we can actually offer something as simple as an aspirin to actually really substantially improve outcomes in patients who have this very serious disease.

Cancer Network: Thank you for taking the time to talk to us about these two interesting secondary prevention studies in colorectal cancer patients.

Dr. Chan: Certainly, it is my pleasure.