Advanced Colorectal Cancer: 3 Drugs Are Better Than One

Patients with advanced colorectal cancer previously only had access to limited treatment options; however, new research presented at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, indicated a combination of 3 targeted drugs could potentially serve as a successful treatment.

Josep Tabemero, head of the medical oncology department at Valld’Hebron University Hospital and director of the Valld’Hebron Institute of Oncology in Barcelona, Spain, and his research team conducted a phase 1 trial to study the effects of the BRAF inhibitor encorafenib combined with cetuximab and epidermal growth factor receptor (EGFR) inhibitor, either with or without alpelisib, an inhibitor of another cancer-inducing pathway known as PI3K.

“Patients with advanced colorectal cancer with tumors that bear BRAF mutations invariably fail to respond meaningfully to standard treatments and ultimately face a dismal prognosis. Further, recent efforts aimed at using a single agent to inhibit BRAF in colorectal tumors have largely disappointed in improving response to therapy in these patients,” Tabemero said.

A total of 54 patients had been enrolled in the dose-finding segment of the trial. Researchers reported tumors had shrunk in 23% of the patients who received both encorafenib and cetuximab, and in 32% of the patients who received a combination of the drug trio.

Results showed that the combination of drugs was generally well tolerated by the patients; adverse side-effects included fatigue, reactions to the infusion, and low phosphate levels in the blood. However, when combined with alpelisib, nausea, diarrhea, skin rashes, high blood sugar levels, and increased levels of lipase can also be potential side effects.

Amyriad of significant cancer-related pathways including the PI3K and WNT are involved in colorectal cancer. According to Tabemero, "This could explain why drugs that target different pathways are more effective when used together."

Tabemero concluded, “While it is still early days and these are preliminary data, this combinatorial strategy is showing improved efficacy, extended progression free survival, with manageable side-effects in patients. This study, therefore, represents a significant step forward in providing metastatic colorectal cancer patients with fresh hope and a new therapeutic avenue.”