The Clinical Efficacy of Dabrafenib Plus Trametinib Combination Treatment in Stage III/Ⅳ BRAF-Mutated Melanoma Volume 12 - Issue 1

Zhao Hongbing¹, Zhang Xifeng², Feng Ting Ting¹ and Li Xiao Rui*¹

• ¹ Department of Oncology, China
• ²Shang Qiu Medical School, China

Received: December 04, 2018;   Published: December 13, 2018

*Corresponding author: Li Xiao Rui, Department of Oncology, Xinxiang, Henan, China

DOI: 10.26717/BJSTR.2018.12.002205

Abstract PDF

The morbidity of cutaneous melanoma has continued to increase in recent years. Patients with stage III disease are at higher risk for recurrence after locoregional resection and many will ultimately die from metastatic melanoma. BRAF inhibitors vemurafenib and dabrafenib have significantly improved progression-free survival (PFS) and overall survival (OS) as single agents compared with cytotoxic chemotherapy. Acquired resistance to BRAF inhibitors inevitably develops, resulting in a median progression-free survival of 6 to 8 months. Several clinical trials with combination treatment of dabrafenib(150 mg twice daily) plus trametinib(2 mg once daily) in stage III/Ⅳ BRAF-mutated melanoma have been reported. These clinical trials identify combination treatment of dabrafenib plus trametinib as front-line therapy in stage III/Ⅳ BRAF-mutated melanoma.

Keywords: Dabrafenib; Trametinib; Braf; Mek; Mutant; Melanoma

The morbidity of cutaneous melanoma has continued to increase in recent years [1]. Patients with stage III disease are at higher risk for recurrence after locoregional resection and many will ultimately die from metastatic melanoma [2]. Oncogenic driver mutations in BRAF are found in approximately 40% to 50% of cutaneous melanomas and induce constitutive activation of the MAPK signaling pathway, driving melanoma growth and progression [3]. BRAF inhibitors vemurafenib and dabrafenib have significantly improved progression-free survival (PFS) and overall survival (OS) as single agents compared with cytotoxic chemotherapy [4,5]. Despite these advances, acquired resistance to BRAF inhibitors inevitably develops, resulting in a median progression-free survival of 6 to 8 months [6].

Mechanisms of acquired resistance include secondary NRAS or MEK mutations [7]. In preclinical models, combined BRAF and MEK inhibition achieves more via abrogation of MAPK signaling, thereby forestalling the development of acquired resistance and suppressing paradoxic activation of the MAPK pathway [8-14]. Several clinical trials with combination treatment of dabrafenib(150mg twice daily) plus trametinib(2mg once daily) in stage III/Ⅳ BRAF-mutated melanoma have been reported. Here, we review the clinical efficacy of these clinical trials. (Inclusion criteria for these studies included age ≥16 years, histologically confirmed BRAFV600E- or BRAFV600K-mutant melanoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2.)

Table 1: The Fundamental Parameters and Efficacy of Clinical Trials.

Table 1 the fundamental parameters and efficacy of clinical trials.

These clinical trials identify combination treatment of dabrafenib(150mg twice daily) plus trametinib(2 mg once daily) as front-line therapy in stage III//Ⅳ BRAF-mutated melanoma.

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