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.

Jen-Hao Yeh,Wei-Chih Su,Ching-Chun Li,Ching-Wen Huang,Yen-Cheng Chen,Jaw-Yuan Wang,Po-Jung Chen,Hsiang-Lin Tsai,Yu-Peng Liu,Tsung-Kun Chang

doi:10.3390/medicina57121339

Abstract

Backgroundand 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.

Highlights

Cases of metastatic colorectal cancer comprise approximately one-fourth of all colorectal cancer (CRC) cases at initial diagnosis, and an additional 20% of CRC patients may present subsequent metachronous metastasis despite treatment [1,2]
We demonstrated the real-world experience of using triplet therapy for BRAF-mutated metastatic colorectal cancer (mCRC) as later lines of salvage therapy in Asian patients
Our findings suggest that triplet therapy appears to be well-tolerated and patients with initial disease control and longer PFS might gain considerable survival benefit, most patients in our study still experienced disease progression

Summary

Introduction

Cases of metastatic colorectal cancer (mCRC) comprise approximately one-fourth of all colorectal cancer (CRC) cases at initial diagnosis, and an additional 20% of CRC patients may present subsequent metachronous metastasis despite treatment [1,2]. Is a well-known biomarker that has an impact on mCRC survival and may affect the response of systemic and targeted therapies. The BRAF mutation is only detected in 5%–10% of all cases, mCRC patients who are microsatellite-stable with the BRAF V600E mutation have worse survival and response to anti-epidermal growth factor receptor (EGFR) agents [9,10]. Patients with BRAF-mutated metastatic colorectal cancer have considerably poorer responses to conventional systemic treatment. 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).

Methods

Results

Conclusion