Scott Kopetz, MD, PhD, FACP
-mutant colorectal cancer (CRC), a subtype that comprises approximately 6% to 7% of patients overall, is an area in need of more effective targeted therapies, said Scott Kopetz, MD, PhD, FACP.
, Kopetz, an associate professor in the Department of Gastrointestinal Medical Oncology and the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discussed the current treatment landscape of CRC and the importance of molecular subtyping.
OncLive: How would you describe the current CRC treatment landscape?
: This is an area that has been actively developed over the past year. There are a number of molecularly defined subtypes for colon cancer. We're certainly well aware of the idea of KRAS
mutations and NRAS
mutations as being part of [the molecular workup of this disease]. There are novel evolving biomarkers and therapies associated with them.
What are other recent data within BRAF-positive CRC you are particularly excited about?
We also tested encorafenib, binimetinib, and cetuximab. It had a very promising response rate of about 48% with a median PFS of about 8 months. It’s an ongoing randomized phase III trial. Within BRAF
-positive disease, a lot of advances have been made this year. There has been a new addition into the NCCN guidelines, as well as this promising combination.
can also be mutated in other areas besides V600E, and there are some interesting updates in understanding the biology of what we consider to be non-V600E mutations. They don't all behave the same. Again, there have been some interesting data and we hope to see more trials looking at this. These kinds of mutations only affect about 2% of patients with CRC. It's an area of interest.
What other subgroups have been recently addressed?
There have also been developments in HER2
amplification. This is something we've been following in the field for several years. There is increasing evidence that perhaps this is a reason for resistance to EGFR inhibitors. A number of studies have also demonstrated that HER2-amplified tumors are sensitive to combination therapies. Trastuzumab (Herceptin) in combination with pertuzumab (Perjeta) is the one being highlighted the most. There are combinations being tested in Europe with different agents, as well.
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