Scott Kopetz, MD, PhD, FACP, Deputy Chair for Translational Research, Department of Gastrointestinal (GI) Medical Oncology, Professor, Department of Gastrointestinal (GI) Medical Oncology and Leader, Department of Cancer Center Support Grant, GI Program, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.

Scott Kopetz, MD, PhD, FACP, associate professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the rarity of fusions in patients with colorectal cancer (CRC).

Patients with fusions comprise a very small percentage of the overall population of patients with CRC, explains Kopetz. The most common fusions are those in 

. In total, the overall occurrence of fusions in CRC is likely less than 1%, says Kopetz. Because of their rarity, fusions are not routinely tested in practice. Though there is value in their identification, there remains debate over the best way to detect them, Kopetz adds.

Notably, fusions tend to overlap with microsatellite instability (MSI), which is associated with high and durable responses to PD-1 and CTLA-4 blockade. In July 2018, the FDA approved the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) for pediatric and adult patients with MSI-high or mismatch repair deficient metastatic CRC following progression on a fluoropyrimidine, oxaliplatin, and irinotecan.

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Dr. Kopetz on the Rarity of Fusions in CRC

Scott Kopetz, MD, PhD, FACP, associate professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the importance of molecular testing in colorectal cancer (CRC).

The current guidelines suggest that microsatellite instability (MSI) testing should be done in every patient with CRC regardless of stage, Kopetz says. MSI testing is often done by immunohistochemistry, but it can also be done by a polymerase chain reaction test. This has important implications for family members, as MSI status can signal a hereditary risk for CRC. Additionally, it can inform treatment decisions for immunotherapy.

Kopetz says that other tests that should be done are KRAS, NRAS, and BRAF testing—which are all considered standard. HER2 gene amplification testing is starting to be done in some institutions, as HER2 status can provide predictive and prognostic information. Kopetz predicts that HER2 gene amplification testing will become a part of the guidelines in the near future.

Scott Kopetz, MD, PhD, FACP, associate professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the importance of molecular testing in colorectal cancer.
 

Dr. Kopetz on the Importance of Molecular Testing in CRC

Scott Kopetz, MD, PhD, FACP, associate professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses triplet therapy for patients with 

Although there have been many advances in the treatment landscape of 

-mutant CRC, there is still room for improvement, says Kopetz. Currently, a promising triplet therapy of BRAF, MEK, and EGFR inhibitors is being studied in this population.

In the randomized phase III BEACON study, the triplet of binimetinib, encorafenib, and cetuximab (Erbitux), is being evaluated in patients with metastatic 

V600E CRC whose disease has progressed after 1 or 2 prior regimens. Kopetz says that this combination demonstrated a promising response rate of about 48%, with a median progression-free survival of about 8 months.

Scott Kopetz, MD, PhD, FACP, associate professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses triplet therapy for patients with BRAF-mutant colorectal cancer

Dr. Kopetz Discusses Triplet Therapy for BRAF-Mutant CRC

Scott Kopetz, MD, PhD, FACP, associate professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the treatment of patients with 

About 5% of patients with metastatic CRC harbor a 

mutation. Overall, the subgroup has a poor prognosis, as these tumors are very aggressive and the therapies available are not effective, Kopetz says. Most patients who harbor a 

Over the last year, there was a recent addition to the standard-of-care regimen for these patients as a result of the findings from the SWOG 1406 trial. This randomized study investigated irinotecan and cetuximab (Erbitux) with or without vemurafenib (Zelboraf) in 

-mutant metastatic CRC. Results showed an improvement in progression-free survival, and had improved disease control rates, Kopetz says. This regimen is now considered a standard therapy for second- and third-line treatment.

Scott Kopetz, MD, PhD, FACP, associate professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the treatment of patients with BRAF-mutant colorectal cancer. 

Scott Kopetz, MD, PhD, FACP

Articles

Dr. Kopetz on the Rarity of Fusions in CRC

Dr. Kopetz on the Importance of Molecular Testing in CRC

Dr. Kopetz Discusses Triplet Therapy for BRAF-Mutant CRC

Dr. Kopetz Discusses the Treatment of BRAF-Mutant CRC