The researchers from multicenter research institutions published a study in the New England Journal of Research, revealing that a combination of Encorafenib, Binimetinib, and Cetuximab could prolong the overall survival among patients with BRAF mutated colorectal cancer.
Combination therapy is a treatment that uses more than one medication to achieve better therapeutic efficacy. It is not a novel idea since we have already used various medicinal herbs as a whole to treat a single disease in ancient times. In the research field of cancer, however, combination therapy is still at an early stage and will be increasingly popular with new antitumor agents emerging day by day.
Advantages of combination therapy
There are some advantages of using combination therapy in cancer treatment:
- Slow the development of drug resistance
- Reduce drug side effects and drug-related complications
- Help improve drug bioavailability
However, despite combined advantages, some adverse responses may happen. Therefore, researchers are always cautious and detailed clinical trials are conducted to verify the feasibility of a combination before this kind of combination therapy is widely used to treat cancer and diseases.
A triplet therapy designed for BRAF-mutated colorectal cancer
BRAF mutations common in different types of cancer, and BRAF inhibitors can be used to treat BRAF mutated melanoma. BRAF inhibitors alone have limited activity in BRAF V600E-mutated colorectal cancer.
To find the best combination regimen involves rounds of collocation. Previous clinical studies revealed that BRAF inhibitors showed increased inhibitory activity when combined with anti-EGRF(epidermal growth factor receptor)monoclonal antibodies. Also, some researchers found that combined inhibition of BRAF and mitogen-activated protein kinase (MAPK) kinase (MEK) was more effective than BRAF inhibitors combined with anti-EGFR agents. Furthermore, subsequent studies showed that combined BRAF inhibitors with both anti-EGFR monoclonal antibodies and MEK inhibitors showed strong inhibitory activity.
Based on these findings, researchers of the study explored the therapeutic efficacy of a triplet-agent therapy which included the BRAF inhibitor Encorafenib, the EGFR inhibitor Cetuximab, and the MEK inhibitor Binimetinib.
In order to compare the therapeutic effects, the study also included the doublet-therapy group (encorafenib and cetuximab) and the control group (either cetuximab and irinotecan or cetuximab and FOLFIRI)
A triple-combination therapy of encorafenib, binimetinib, and cetuximab
The primary endpoints were overall survival and objective response rate in the triplet-therapy group as compared with the control group. The study results showed that the median overall survival was 9.0 months in the triplet-therapy group, 3.6 months longer than that in the control group. The confirmed response rate was 26% in the triplet-therapy group and 2% in the control group, respectively.
One of the secondary endpoints was overall survival in the doublet-therapy group as compared with the control group. The median overall survival in the doublet-therapy group was 8.4 months. The risk of death in the doublet-therapy group was significantly lower than that in the control group.
The study also investigated the progression-free survival and safety as secondary endpoints in all groups.
The results showed that the progression-free survival was significantly longer in both the triplet-therapy group and the doublet-therapy group than in that group. The median progression-free survival was 4.3 months in the triplet-therapy group, 4.2 months in the doublet-therapy group, and 1.5 months in the control group.
Some common adverse reactions in combination therapy include gastrointestinal-related and skin-related events such as diarrhea, nausea, vomiting, and dermatitis. Adverse events of grade 3 or higher were observed in 58% of patients in the triplet-therapy group, 50% in the doublet-therapy group, and 61% in the control group. Moreover, the triplet-therapy group showed the lowest discontinuation of therapy of 7%.
Generally, these statistical analyses revealed that a triple regimen of encorafenib, binimetinib, and cetuximab can achieve the best therapeutic effects in patients with BRAF V600E–mutated metastatic colorectal cancer. The findings of the study could provide some insight for the improvement of the current treatment of colorectal cancer.