ASCO GI: Latest Treatments and Research in Gastrointestinal Cancers

Cathy Eng, MD

Today, ahead of the American Society of Clinical Oncology (ASCO) 2013 Gastrointestinal (GI) Cancers Symposium held in San Francisco January 24–26, we speak with Dr. Cathy Eng, associate professor in the department of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center in Houston, Texas, and one of the members of the symposium’s steering committee. Dr. Eng specializes in colorectal, anal, and appendiceal cancers and takes part in many earlier-stage clinical trials for treatment of these cancers, as well as in research to identify genetic predictors of clinical outcomes for these cancers.

-Interviewed by Anna Azvolinsky, PhD

Cancer Network: Dr. Eng, this year, ziv-aflibercept (Zaltrap), an angiogenesis inhibitor, was approved in combination with chemotherapy for advanced colorectal patients, as well as regorafenib (Stivarga), a tyrosine kinase inhibitor. How do you see these therapies used for colorectal patients in the context of the therapies that are already available?

Dr. Eng: I think right now, these two drugs in particular, were just recently approved, so I think a lot of individuals are just becoming familiar with the appropriate use of either agent and trying to figure out how best to incorporate these into the regular treatment regimen. Aflibercept, obviously, has quite a bit of competition with bevacizumab (Avastin) because that has been utilized now for several years, and people tend to take a while to adapt to new treatment options. People also tend to continue to utilize things that they are more comfortable with, especially regarding toxicities. So, I think that at some point, aflibercept will have its own role in the second-line setting, it is just going to take a while to get people to utilize it and choose it over bevacizumab. Regarding regorafenib, it is currently approved as a single agent in a very different setting, so it really has no competition with any other agent at this time, because it is for patients who have failed all prior lines of therapy, and it is unique in the sense that it is an oral agent. It does have some side effects, so people have to be cautious because they are not familiar with this agent.

Cancer Network: Are there other exciting advances in the treatment or diagnosis of colorectal cancers that have occurred in the last year to highlight, or perhaps exciting clinical trials that are still in progress that you are looking forward to?

Dr. Eng: Most of the trials that are interesting are still in phase I or phase II of development. One of the trials that we won’t yet have the results from is a phase III trial, international study looking at 3 vs 6 months of adjuvant FOLFOX; I think that is very intriguing for many people because of the toxicity associated with prolonged platinum therapy and the development of neuropathy. But, because it is an adjuvant study, we still have a few years before we see the final results. I know many individuals and their patients and caregivers are very interested in the results of this trial, but that data is quite a bit ahead of us. There are lots of new interesting mechanisms of action, but they are still fairly early in development and we will have to see the early-stage trial results before we know if these are promising.

Cancer Network: What is one example of a mechanism of action that has a scientific rationale backing it for colorectal cancer?

Dr. Eng: There are several agents-MEK inhibitors, PI3K inhibitors-these are all of interest, but whether they have a definitive role in colorectal cancer treatment has yet to be determined. That is why people are trying to characterize patients’ tumors in a more appropriate fashion, to see if these newer drugs or combinations of drugs are appropriate for a patient.

Cancer Network: As someone who studies the genetic variants that may identify patients with a better or worse clinical outcome, have there been recent advances in predictors of these outcomes?

Dr. Eng: We don’t have anything specific right now. Even if you have a BRAF mutation, which many of us know is believed to be a poor prognostic indicator, we don’t have any phase III studies that are addressing this at this time. Once again, these drugs are still early in development in various combinations with other biologics or in combination with chemotherapy. It is still early. This is why the upcoming ASCO GI meeting is important to see what is up-and-coming and what has potential.

Cancer Network: As more targeted agents such as regorafenib are approved, how do you see the genetic characterization of patients’ colorectal cancers evolving? Are more patients now already being genotyped or is this still mainly occurring at academic centers?

Dr. Eng: I see that a lot of patients are actually spending their own money and sending the samples out to various corporations and trying to get their tumor genotyped. There are a lot of competitors out there, a lot of institutions such as our own institution here; MD Anderson has a very large lab for genotyping. A lot of individuals are seeking the information, a lot of physicians are seeking it for their patients; I think that it is eventually going to be a standard of care. The issue right now is payment for these costly tests and also whether or not you have the appropriate tissue specimen. Ideally, you would want to have the most recent site of metastatic disease biopsied and evaluated, but in the majority of individuals, insurance companies will not pay for that, or even if you are part of a clinical trial, there is not necessarily funding for fresh tissue biopsying for patients. People tend to use archival tissue specimen or their most recent surgical resection specimen either from a biopsy or from an actual surgical specimen, but it is not likely that people are getting the most recent metastatic site resected. We know that patients do become resistant to certain therapies over time and that is because their underlying tumor biology changes, and we need to understand that and characterize that, but funding is always an issue.

Cancer Network: Immunotherapies are really moving forward in treating cancers, yet there have not been success stories of immunotherapies for treatment of colorectal cancer and other GI cancers. How do you see the role for immunotherapies for colorectal cancer?

Dr. Eng: I would say there is certainly great interest and a lot of people want to look at stem cell work, but it is very early on in development in colorectal cancer in comparison to other malignancies. There have been a lot of attempts at this in the past that have failed, unfortunately, but I think that this type of work needs to continue because we want to understand the tumor biology, understanding how the patient’s own immune system, cytokines, and inflammation impact how a patient responds to treatment, whether this impacts chemotherapy, radiation therapy, etc.

Cancer Network: Thank you so much for joining us today, Dr. Eng.

Dr. Eng: Sure!