by Dr. C.H. Weaver M.D. Medical Editor updated 4/2019
Breakthrough Therapy Designation was awarded from the U.S. Food and Drug Administration for a novel precision cancer medicine treatment regimen for metastatic colon cancer. The new treatment combines the BRAF and MEK inhibitors Bravtovi™(encorafenib), and Mektovi®(binimetinib) with cetuximab for the treatment of patients with BRAFV600E-mutant metastatic colorectal cancer (mCRC).(1)
Breakthrough Therapy Designation is an FDA process designed to expedite the development and review of drugs that are intended to treat a serious condition where preliminary clinical evidence indicates that they may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. Study results were updated in the J Clin Oncol. 2019 March 20.(2)
About Colorectal Cancer
In the U.S. an estimated 140,250 patients will be diagnosed with cancer of the colon or rectum in 2018, and approximately 50,000 are estimated to die of their disease. BRAF mutations are estimated to occur in 10% to 15% of patients with colorectal cancer and represent a poor prognosis for these patients. The risk of mortality in CRC patients with the BRAFV600E mutation is more than two times higher than for those with wild-type BRAF.(3,4,5)
About BRAFTOVI + MEKTOVI
BRAFTOVI (encorafenib) is an oral small molecule BRAF kinase inhibitor and MEKTOVI (binimetinib) is an oral small molecule MEK inhibitor which target key enzymes in the MAPK signaling pathway. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers including melanoma, colorectal cancer, non-small cell lung cancer, thyroid and others. In the U.S., BRAFTOVI + MEKTOVI are approved for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test.(6,7)
About BEACON CRC Clinical Trial
The BEACON CRC is a clinical trial evaluating treatment with BRAFTOVI + MEKTOVI and cetuximab in patients with BRAFV600E-mutant mCRC whose disease has progressed after one or two prior regimens. The BEACON CRC trial directly compares BRAFTOVI in combination with cetuximab with or without MEKTOVI compared to cetuximab and irinotecan-based therapy. The trial is being conducted at over 200 investigational sites in North America, South America, Europe and the Asia Pacific region.
Data leading to the FDA approval was presented at the ESMO 20th World Congress on Gastrointestinal Cancer. The results of ongoing randomized Phase 3 BEACON clinical demonstrated that:
- The 3 drug combination was generally well-tolerated with no unexpected side effects.
- Overall response rate was 48% and among the 17 patients who received only one prior line of therapy.
- Average time to cancer progression for patients treated with the triplet was 8 months.
- Average overall survival is 15.3 months with a median follow-up duration of 18.2 months (range, 16.6-19.8 months).
- One-year overall survival rate was 62%.
Several precision cancer medicines are now available for the treatment of advanced colon cancer. BRAFTOVI + MEKTOVI represent advances in precision therapies targeting the hard to treat BRAFV600E-mutation and will expand the treatment options for this poor prognosis group of patients once approved
- J Clin Oncol**.** 2019 March 20. Epub ahead of print).
- De Roock et al., Lancet Oncol, 2010
- Global Cancer Facts & Figures 3rd Edition. American Cancer Society. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/global-cancer-facts-and-figures/global-cancer-facts-and-figures-3rd-edition.pdf. Accessed January 2018.
- Cancer Facts & Figures 2018. American Cancer Society. Available at: . Accessed January 2018.
- Safaee Ardekani G, Jafarnejad SM, Tan L, et al. The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and meta-analysis. PLoS One. 2012;7(10):e47054.