News about the BEACON trial, a clinical trial offering a triplet combination for metastatic colon cancer and rectal cancer patients with BRAF V600e.
April 2020 Update:
The Federal Drug Administration announced on April 8, 2020 that the combination of encorafenib and cetuximab was approved for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation detected by an FDA-approved test after prior therapy.
This approval is based on results from the BEACON trial led by Dr. Scott Kopetz, MD, PhD, FACP at M.D. Anderson Cancer Center.
At GIASCO 2020, Dr. Kopetz presented updated results from the BEACON trial, highlighting that patients who were given encorafenib and cetuximab, with or without binimetinib, had better quality of life than patients who received irinotecan plus cetuximab or FOLFIRI. Patients on the doublet (cetuximab + encorafenib) had a 46% reduction in risk, compared to those on the triplet (cetuximab + encorafenib + binimetinib) who had 44-45% reduction in risk.
In October 2019, researchers presented data showing the overall survival on the triplet was 9.0 months and 8.4 months on the doublet combination. Ultimately, researchers decided to submit the doublet to the FDA for approval versus the triplet based on similar outcomes and slightly better quality of life.
According to Dr. Kopetz, “We are excited that a new option will be available for our patients with BRAF V600E mutated colorectal cancer, and look forward to using this treatment as a building block for further innovative treatments in the future.”
In March 2019, the National Comprehensive Cancer Network (NCCN) updated their treatment guidelines to include a specific triplet combination of therapies for patients with BRAF V600e-mutated colorectal cancer. This is for patients who’ve already exhausted one to two lines of therapy.
About the triplet combination therapy for BRAF V600e
This triplet combination for BRAF V600e patients includes:
- BRAF inhibitor encorafenib
- MEK inhibitor binimetinib
- EGFR inhibition using cetuximab or panitumumab
The announcement was made on the heels of the 2019 Gastrointestinal Symposium (GIASCO).
Researchers presented results from the BEACON study, specifically the safety lead-in, which is an initial part of the phase III trial, looking at the highest drug dose patients can tolerate at GIASCO 2019. The BEACON trial was led by Dr. Scott Kopetz, M.D., Ph.D., FACP, Associate Professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center.
According to Dr. Kopetz, “We are pleased that patients will now have access to additional effective therapies for BRAF-mutated colorectal cancer. These new standards of care are welcomed options for this aggressive subtype of colorectal cancer. They are the foundation upon which additional novel strategies are being explored in clinical trials, with the goal of even further improvements in outcomes for patients.”
About the BEACON trial for BRAF V600e
Thirty patients with BRAF V600e-mutant metastatic colon cancer or rectal cancer were enrolled in the safety lead-in phase of BEACON.
Patients received the triplet regimen of encorafenib, binimetinib, and cetuximab. The progression-free survival (PFS), meaning the time it took from the start of the treatment for the cancer to grow or spread, was 8 months. The median overall survival (OS), which represents the time at which 50 percent of patients are still alive after a diagnosis or particular treatment was 15.3 months.
Three patients had a complete response, meaning no cancer was detected after the treatment course, and the overall response rate (ORR) was 48%, meaning nearly half of those on this regimen had a partial or complete response to therapy.
BRAF mutations in colorectal cancer patients
BRAF mutations occur in approximately 5-10% of metastatic colorectal cancer patients.
It’s been well-established that patients with a subtype of BRAF, BRAF-V600e mutations, typically have worse outcomes compared to those without the mutation, oftentimes leading to significantly poorer overall survival and disease-free survival.
Historically, there haven’t been many options for this group of patients, but results from the BEACON trial are leading researchers in the right direction.
“As a stage IV colorectal cancer survivor diagnosed with a BRAF V600e mutation, I am very interested in trials such as the BEACON Trial which hold the promise of new therapies targeting BRAF mutations. Because CRC is the second leading cancer killer, this research and CRC research in general is critical to colon and rectal cancer patients and their survival.”
-Karen Wehling, Stage IV rectal cancer survivor
BRAF therapies approved in August 2018
Back in August 2018, the Federal Drug Administration (FDA) announced breakthrough therapy designation for this triplet (encorafenib (BRAF inhibitor) in combination with binimetinib (MEK inhibitor) and cetuximab (EGFR inhibitor)) to treat metastatic colorectal cancer patients with BRAF V600e mutations. The only difference is that the NCCN guidelines also include panitumumab as an option for EGFR inhibition as well.
Breakthrough therapy designation means that a drug with potential to treat a serious illness is developed and reviewed by the FDA quicker than normal based on the initial evidence that it will have clinical significance and improve treatment and care for patients.
With the recent news that this triplet therapy combination from the BEACON trial will be added to the NCCN guidelines and receive an FDA breakthrough therapy designation, those with metastatic colon cancer or rectal cancers harboring the BRAF V600e mutation have newfound hope.
Did you know: NCCN recommendations and FDA-approved drug indications aren’t always the same. For example, according to this study, “NCCN expert guideline panels recommended additional indications beyond the FDA approved indications 39% of the time” among new drugs approved from 2011-2015. A drug indication means a drug is being used for the treatment of the disease it was intended to treat. A drug which has received FDA approval for one condition may be included in the NCCN guidelines for other conditions as well. The use of off-label drugs for oncology is common.
The future of BRAF 600e research
Research is the platform that drives the future of cancer treatment. Cancer research lead us to this updated news!
Fight CRC will continue to actively follow the results of the phase III BEACON trial, and we will provide updates on the latest science leading to new discoveries.
To help uncover more hope for patients and new treatment options, please consider partnering with us by making a contribution to our Research Fund.