Abstract
PurposeTo investigate the safety and efficacy of dabrafenib and trametinib combination therapy for BRAF V600 mutation-positive unresectable and metastatic melanoma in over 100 Japanese patients of a real-world clinical setting.PatientsThe surveillance period of interim post-marketing surveillance (PMS) analysis was from June 2016 to November 2018, and 112 patients with unresectable and metastatic BRAF V600 melanoma who received dabrafenib and trametinib were enrolled.ResultsThe safety analysis set included 112 patients whom almost all patients had stage IV disease (n = 97, 86.61%) with an Eastern Cooperative Oncology Group performance status 0 or 1 (n = 102, 91.07%), and mean (standard deviation) lactate dehydrogenase level was 354.3 (456.4) U/L (n = 105) at baseline. Median daily dose of dabrafenib was 300.0 mg/day (118–300), and median daily dose of trametinib was 2.00 mg/day (1.0–4.0). Adverse drug reactions (ADRs) were reported in 84 patients (75%), and common ADRs (incidence ≥ 5%) were pyrexia (n = 49, 43.75%), hepatic function abnormal (n = 11, 9.82%), rash and blood creatine phosphokinase increased (n = 9 each, 8.04%), and erythema nodosum (n = 6, 5.36%). Majority of ADRs reported in this study were consistent with that reported in previous trials. In the efficacy analysis set of 110 patients, the objective response rate was 55.45% (95% confidence interval 45.67–64.93%), and median progression-free survival was 384.0 days (251.0 days-not reached).ConclusionsNo new safety or efficacy concerns were observed in this interim PMS analysis in Japanese patients with unresectable and metastatic melanoma with BRAF gene mutation who received dabrafenib and trametinib combination therapy.
Highlights
Melanomas are malignant tumors arising from pigment cells/melanocytes [1]
The disease is common in Caucasians, with more than 76,000 new cases and 9000 deaths reported in the US in 2012 [2], whereas the disease is less common in Asians, including the Japanese, with approximately 1–2 new cases reported per 100,000 people per year [3] and about 4000 patients reported with melanoma in 2016 in Japan [4]
In the post-marketing surveillance (PMS) of dabrafenib and trametinib, 372 patients were registered at 118 medical sites across Japan since the start of the survey (June 2016), and data of 118 patients were locked until November 2018
Summary
Melanomas are malignant tumors arising from pigment cells/melanocytes [1]. Melanomas are mostly of cutaneous origin, they can occur at a low frequency in various extra-cutaneous sites, where non-cutaneous melanocytes are present, including the respiratory, gastrointestinal, and genitourinary sites [1]. Metastatic melanoma has been considered as one of the most therapeutically challenging malignancies [5, 6]. Since the discovery of BRAF V600 somatic missense mutations in approximately 50% of malignant melanomas and at a lower frequency in a wide range of human cancers [7], there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma, with high response rates [5, 6]. BRAF mutations result in constitutive activation of the BRAF kinase protein, thereby promoting hyperactivation of the mitogen-activated protein kinase (MAPK) signaling pathway, which includes mitogen-activated protein kinase kinase (MEK), an essential regulator of cell proliferation and survival [8]
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