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Therapies in Development to Improve Outcomes in BRAF-Mutated CRC

Danielle Bucco
Published: Monday, Sep 25, 2017

Tim G. Larson, MD
Tim G. Larson, MD
Patients with BRAF-mutated colorectal cancer (CRC) tend to have a poor prognosis and often do not respond to some of the currently available therapies, according to Tim G. Larson, MD.

The randomized phase III BEACON study evaluated both the combination of binimetinib, encorafenib, and cetuximab (Erbitux), and encorafenib and cetuximab in patients with BRAF V600E metastatic CRC whose disease progressed after 1 or 2 prior regimens in the metastatic setting.

Preliminary efficacy data support the benefit of adding binimetinib to encorafenib and cetuximab. The combination was found to be well tolerated, providing hope for this challenging patient population.

“This trial is offering some promising therapies to this patient population,” said Larson. “If I have a patient with a BRAF mutation, this is a trial that I would be interested in enrolling them to.”  

In an interview during the 2017 OncLive® State of the Science SummitTM on GI Malignancies, Larson, who is of Minnesota Oncology, discussed emerging data involving immunotherapy for patients with microsatellite instability (MSI)/microsatellite stable (MSS) CRC and highlighted some of the identified molecular mutations in patients with CRC.

OncLive: Please provide an overview of your presentation.

Larson: Dr Axel Grothey covered the initial treatment of patients with mCRC and I discussed everything after that. Most of my talk was on the newer things that might be breaking into the clinic if they pan out, such as novel treatments and promising regimens that we heard about at the 2017 ESMO Congress and 2017 ASCO Annual Meeting.

Is there a specific treatment that stands out to you as being the most promising?

Everyone is interested in immunotherapies. While the MSI-high population is a small percentage of CRC, I believe that patients really could benefit from these therapies. We haven’t cracked the nut yet for the MSS population, which is about 95% of the metastatic CRC population. I presented data from investigators using unique combinations or unique novel molecules, which might be the first times where we could be making some progress. That is the most exciting area.

What combinations are currently being explored with immunotherapy?

I had one slide that looked at a variety of the drugs that investigators are currently using, such as biologics and targeted therapies. I allude to this one study done by Dr Tabernero, which looked at a novel antibody that links T cells to the tumor. Overall, there are a variety of approaches. 

What ongoing clinical trials hold the most promise?

One that will be opened at University of Rochester is called the BEACON trial. Dr Axel Grothey is the site investigator. It is for BRAF-mutated patients, which make up a small group of patients with CRC who have poor prognoses and do not respond to certain agents that we use otherwise. They have been a challenge. This trial is offering some promising therapies to this patient population.


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