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

Mini Review

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.

Result

Table 1 the fundamental parameters and efficacy of clinical trials.

Conclusion

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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