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Grothey Highlights Biomarker Research in CRC

Danielle Bucco
Published: Monday, Sep 25, 2017

Axel Grothey, MD
Axel Grothey, MD
Identifying biomarkers for patients with colorectal cancer (CRC) continues to be a topic of discussion among researchers in the field, according to Axel Grothey, MD.

“There are various biomarkers, such as RAS and BRAF. We also do microsatellite-instability (MSI)-high testing to select patients for immunotherapy,” said Grothey.

Additionally, tumor sidedness might impact response to treatment, he adds. Researchers are attempting to determine biological and genetic explanations for the inferiority of right-sided CRC.

“The European and the American guidelines have come to different conclusions. I believe there is a golden medium between those and we can utilize the sidedness data to help with improvements for treatment,” said Grothey.

In an interview with OncLive® at the 2017 State of the Science SummitTM on GI Malignancies, Grothey, a medical oncologist at Mayo Clinic, discussed current first-line treatments for patients with CRC and highlighted the importance of developing biomarkers for this population.

OncLive: Please provide an overview of your presentation.

Grothey: I talked about first-line treatment for colorectal cancer. First of all, there is an abundance of new and established drugs that are available right now. The key question that we have is, “Which patient should receive which treatment?” There are some theories, but we are more interested in looking at biomarker-driven decisions.

We are also wondering how can the location of the tumor, whether it is left or right, help us to decide whether we use cetuximab (Erbitux) or a VEGF inhibitor like bevacizumab (Avastin) as part of the treatment plan for our patients. There are data right now that clearly indicates that right-sided tumors do not benefit from certain therapies. We should use bevacizumab in right-sided tumors.

The European and the American guidelines have come to different conclusions. I believe there is a golden medium between those and we can utilize the sidedness data to help with improvements for treatment.

Can you discuss available and potential biomarkers for these patients?

There are various biomarkers, such as RAS and BRAF. We also do MSI testing to select patients for immunotherapy.

We decided to use HER2 screening amplification, like in breast cancer and gastric cancer, for all patients with metastatic CRC because there are more data showing that HER2 amplification is associated with a negative predictive marker for panitumumab (Vectibix) and cetuximab. It can also help us select patients for HER2-targeted therapies, which are available but they are not necessarily approved yet. These potential targeted therapies are being investigated in clinical trials.

What is some ongoing research that you find promising?

First of all, there are several trials ongoing, which look at making tumors that are not yet immune responsive become immune responsive. Everyone is raving about immunotherapy, it’s everywhere. Unfortunately, in metastatic CRC it’s about 4% to 5% of patients who really benefit from immunotherapy as we know it now.

The addition of immunotherapy to chemotherapy might help us generally change the tumor type, meaning the tumor-immune cells get into the tumor itself by adding other agents to immunotherapy, such as MEK inhibitors or bi-specific antibodies. Those are ongoing experimental trial ideas.

For the majority of patients right now, this will still take some time for all this research to materialize. The agents such as cetuximab, panitumumab, or bevacizumab will not go away.

How do we sequence these agents?

Sequencing of agents is important because eventually patients benefit from being exposed to all active agents. The first-line treatment determines the second-line and third-line treatments. There are some personal preferences that people have developed. There are some patient characteristics where you might want to avoid certain side effect profiles in certain drugs. Eventually though, patients will get exposed to mostly all agents and I believe they should be.

With chemotherapy, it is clear that we move from one therapy to another. For the biologics, like the VEGF inhibitors, the situation is not that clear because we know that these agents work even when patients have progression of disease. For instance, continuation of bevacizumab during progression is one of the established treatment options with survival benefits. This is an interesting phenomenon.

We are learning how to deal with markers of secondary resistance. For the majority of patients, the tumor might respond to the treatment initially but then stops responding. No patient will respond forever on these treatments, which is a problem.




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