BRAF, MEK, and EGFR Triplet Inhibitors as Salvage Therapy in BRAF-Mutated Metastatic Colorectal Cancer—A Case Series Study Target Therapy of BRAF-Mutated mCRC

Abstract

Background and objectives: Patients with BRAF-mutated metastatic colorectal cancer have considerably poorer responses to conventional systemic treatment. The real-world effects of triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in Asia have not been well-reported. Materials and Methods: This single-center case series included patients with BRAF-mutated metastatic colorectal cancer undergoing triplet therapy after failure of prior systemic treatment from 2016 to 2020. The primary outcome was progression-free survival, and secondary outcomes were overall survival, response rate, disease control rate, and adverse events. Results: Nine eligible patients with BRAF-mutated metastatic colorectal cancer receiving triplet therapy were enrolled, with a median follow-up time of 14.5 months (range, 1–26). Most patients (88.8%) had two or more prior systemic treatments, and the triplet regimen was mainly dabrafenib, trametinib, and panitumumab. The overall response rate and disease control rate were 11.1% and 33.3%, respectively. Median progression-free survival and overall survival were 2.9 and 7.4 months, respectively, and a trend toward better overall survival was found with left-sided metastatic colorectal cancer compared with right-sided disease (9.2 vs. 6.9 months, p = 0.093). Adverse events were mostly Grade 1–2, including nausea, hypertension, gastrointestinal symptoms, and skin disorders. Conclusions: In this single-center case series, triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in BRAF-mutated metastatic colorectal cancer had an acceptable safety profile and reasonable efficacy.

Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension—Mechanisms and Mitigation

“…The expanding development and application of BRAF-MEK inhibitors has led to trials of triplet treatment combinations such as with immune checkpoint inhibitors, 104,105 PARP (poly [ADP ribose] polymerase) inhibitors (PARPi) and EGFR inhibitors 106 which may improve resistance to BRAF-MEK available treatments and efficacy for patients. Although limited, there are data from trials in advanced BRAF-mutated melanoma, which compared addition of pembrolizumab or placebo to a combination of dabrafenib and trametinib, of higher incidence of grade 3 hypertension (8.3%) in the triplet therapy group compared with the placebo group (3.3%).…”

BRAF Mutations in Colorectal Liver Metastases: Prognostic Implications and Potential Therapeutic Strategies

“…In the past, triple therapy with BRAF , MEK, and EGRF inhibitors has mostly been used in clinical studies in European and American populations, whereas the safety and efficacy of triple therapy in Asian populations have not been well reported. In December 2021, a single-center study was conducted on an Asian population [ 61 ]. Nine eligible mCRC patients with BRAF mutations were enrolled and received triple therapy, with a median follow-up of 14.5 months (1–26 months).…”

Gut microbiota composition in chemotherapy and targeted therapy of patients with metastatic colorectal cancer

“…Although the overall survival (OS) of patients with CRC has increased, the treatment of metastatic CRC (mCRC) remains a clinical challenge. For example, patients with mCRC and BRAF mutation exhibited a poor response to systemic treatment and had an unfavorable prognosis (6,7). The RAS gene mutation is a crucial factor for CRC tumorigenesis, invasion, and metastasis and can thus serve as a therapeutic agent (8).…”