Bert O’Neil, MD
The development of molecular testing and next-generation sequencing throughout the oncology space has also been applied to gastrointestinal (GI) cancers management, in an effort to better identify molecular alterations and optimize treatment decisions.
“We are trying to get to a point where we no longer think of a cancer type based on where it came from, but rather what type of cancer it is genetically,” says Bert H. O’Neil, MD.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Gastrointestinal Cancers, O’Neil, the Joseph W. and Jackie J. Cusick Professor of Oncology, professor of medicine, and director of the Phase I and Gastrointestinal Oncology Programs at Indiana University, discussed the role of molecular testing throughout GI cancers and highlighted the current and developing treatment landscape for patients with colorectal cancer (CRC).
OncLive: You spoke on precision medicine in GI cancers as well as a specific focus on mCRC. How have you seen the GI cancers paradigm evolve?
We are now well into this area of precision medicine, which involves genetic sequencing of tumors to look for treatment options that we might not have considered for patients with a particular tumor type in the past. It is an exciting time.
This is a big paradigm shift for us. In my talk, we discussed the basics of testing, how we test, and what kinds of results are out there so far. This is an area that is going to keep evolving as we get more drugs and as we define more genetic abnormalities. There is a lot of potential for future growth and it is something that people are generally familiar with but is also a good area to learn the newest data.
What are the differences between targeted and expanded testing and when might it be better to use one over the other?
If you are early in the treatment of a disease where you know there is a defined set of options that work well, then a targeted panel of genes is what makes the most sense. In patients beyond that initial set of treatments, where we are starting to get into an area of limited options, then we want to look more broadly because we are “hunting” for something that we wouldn't normally think of. In a patient with refractory cancer—or you could almost argue in any type of cancer—it makes sense to do a broad panel to get as much information as possible to find a treatment choice for someone who may not have one.
Are liquid biopsies something that we are prioritizing in GI cancers?
Liquid biopsies in GI cancers is an interesting area right now. Unlike lung cancer, we do not tend to have the problem of not having enough tissue. In some ways, I would argue that liquid biopsies are not as necessary as they are in lung cancer, where it is less safe to biopsy patients and take large pieces of tissue.
On the other hand, we are starting to see interesting data when you follow the genetic mutations in the plasma as patients are being treated. We see new mutations arise and those may help us make decisions about future therapy. We are not quite there yet, as it is still an evolving area of research. However, its clinical applicability in GI cancers is still unclear.
How else are we evolving with precision medicine in GI cancers?
GI cancers are arguably tougher than the other cancer types in terms of finding usable genetic hits. That is probably because, from CRC, we know that there is a huge frequency of these mutations that we do not know what to do with, such as RAS
. Many of those mutations do not have tyrosine kinase inhibitors that we can use, so it is a challenge. We are at a point where we do not necessarily need to find the mutations, but we need to find the drugs for the mutations we already know about.
Can you give an overview of your other presentation, which was on CRC?
We discussed where we are in terms of patient selection for second-line therapy. This includes clinical factors, such as RAS
mutations, which is something we have known about for quite some time. We have talked about first-line data comparing EGFR-targeted antibodies and the VEGF-directed antibody strategies.