Abstract
ObjectivesTo examine the long-term survival outcome of dabrafenib in combination with trametinib in Chinese patients with unresectable or metastatic acral/cutaneous melanoma with BRAF-V600 mutation and to explore potential predictors of effectiveness.MethodsThis was a long-term follow-up of Chinese patients with unresectable or metastatic BRAF V600-mutant acral/cutaneous melanoma administered dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) in an open-label, multicenter, single-arm, phase IIa study (NCT02083354). Efficacy endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). The impacts of baseline characteristics on PFS and OS were analyzed.ResultsA total of sixty patients were included. The median age was 48 years, and 24 patients (40.0%) were male. Totally 12 individuals (20.0%) had acral melanoma, and 45 (75.0%) had failed previous systemic therapy. Up to July 2020, the median duration of follow-up was 37.0 (95% confidence interval [CI] 29.1-44.9) months. The updated ORR was 71.7% (95%CI 60.3%-83.1%). The 3-year OS rate was 28.8% (95%CI 19.1-43.6%) in the overall population, and 35.7% (95%CI 15.5–82.4%) in acral melanoma patients. The median DOR was 7.5 months (95%CI 4.5 to 10.5). Baseline normal lactic dehydrogenase (LDH), metastatic organ sites<3 and complete response to combination therapy with dabrafenib plus trametinib were associated with improved PFS and OS.ConclusionDabrafenib combined with trametinib confer long-term survival in Chinese patients with BRAF V600-mutant, unresectable or metastatic acral/cutaneous melanoma.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT02083354, identifier NCT02083354.
Highlights
The incidence of melanoma is only 0.9 per 100,000 persons in China, it has been increasing for the past 20 years [1]
Eligible patients were ≥18 years of age, with histopathologically confirmed stage IIIc or IV melanoma, BRAF V600 mutation according to the central reference laboratory, at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [16], Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate organ function
With an additional 28 months of follow-up since the last analysis, no new safety issues were reported. This 3-year analysis showed that in Chinese patients with unresectable or metastatic BRAF V600-mutant melanoma, median overall survival (OS) and 3-year OS rate were 17.6 months and 23%, respectively, after treatment with dabrafenib plus trametinib. These data, which represent the longest follow-up of dabrafenib plus trametinib in Chinese melanoma patients to date, confirm the durable antitumor activity and safety of D+T in advanced and metastatic acral/cutaneous melanoma
Summary
The incidence of melanoma is only 0.9 per 100,000 persons in China, it has been increasing for the past 20 years [1]. BRAF mutations were reported in 50% cutaneous melanoma and 15% acral melanoma cases; the latter is the most common subtype in Chinese melanoma patients [3, 4]. Major strides have been made in the treatment of advanced melanoma with BRAF mutation in recent years. PD-1 blockade was effective regardless of the patient’s BRAF mutation status in some trials [12, 13], existing data demonstrated an ORR of 15% in Chinese BRAF V600-mutant melanoma patients treated with pembrolizumab [14]
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