Combining therapies for a treatment-resistant BRAF-mutant colorectal cancer

This study reviewed therapies under development for the treatment of a rare form of colorectal cancer. It was found that the combination of 2 or more drug types may be the most effective treatment regime. 

10% of colorectal cancer (CRC) patients have a rare genetic form of the disease. This form of CRC is called BRAF mutant CRC. It is associated with poor prognosis and increases mortality risk two-fold. 

It is thought that this form of CRC uses different mechanisms to prevent treatments from working. Different types of biological therapies, such as cetuximab (Erbitux) and panitumubab (Vectibix), target different mechanisms. Combining different drug types may be the most effective treatment approach.

This study reviewed biological therapies under development for the treatment of BRAF mutant CRCs. The authors analyzed the results of over 40 studies.

43 patients with BRAF mutant CRC took part in one study. The patients were treated with dabrafenib (Tafinlar) and trametinib (Mekinist). 1 patient achieved a complete response (no sign of cancer) lasting for more than 3 years. 12% of patients achieved a partial response (decrease in tumor size). 51% achieved disease stability. 23% remained on the study for more than 6 months.

In another study, 27 patients were treated with vemurafenib (Zelboraf) and cetuximab. Mid-trial results showed that 7% of patients responded partially and 52% achieved disease stability.

One study consisted of 15 patients treated with vemurafenib and panitumubab (Vectibix). 13% of patients showed a partial response to treatment. 73% achieved disease stability.

In another study, 26 patients were treated with encorafenib (LGX818) and cetuximab. 23% of patients responded to treatment.  73% achieved disease stability.

Studies investigating the combination of drug treatments with chemotherapy or therapies targeting the immune system are ongoing.  

The authors suggested that the best treatment approach may involve the combination of 3 different drug types. It was noted that the identification of patient groups which will respond to treatment will lead to further improvements. 

 The author has received consulting fees from Glaxo Smith Kline and Genentech, which produce some drugs used to treat CRC.