Patients with early negativization of BRAF V600 in tumor-derived circulating cell-free DNA (cfDNA) have excellent prognosis, which is comparable to those with negative BRAF in pretreatment cfDNA, according to a study presented at American Association for Cancer Research (AACR) Annual Meeting 2016.1

Previous research has demonstrated median overall survival was 7 months among patients with positive BRAF pretreatment cfDNA compared with 22 months for those with negative BRAF pretreatment cfDNA.

Based on these findings, researchers sought to determine the prognostic value of BRAF V600 mutation in pretreatment cfDNA, the change in mutation status at the time of first evaluation, and the correlation of BRAF cfDNA dynamics with clinical evolution.

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For the prospective study, researchers assessed 159 plasma and serum sample collected from 66 patients with stage 4 BRAF-mutant melanoma before and during treatment until disease progression.

Results showed that median overall survival was 6.4 months (95% CI, 10.9 – 23.6) and 17 months (95% CI, 3.5 – 9.2) for patients with positive and negative BRAF pretreatment cfDNA, respectively (P = .06).

Further, researchers observed significant differences in overall survival according to BRAF early-cfDNA negativization. Median survival was 4.7 months (95% CI, 1.2 – 8.1) in patients with persistence of BRAF in cfDNA, not reached in those with BRAF early-cfDNA negativization, and 22 months (95% CI, 0.6 – 43.9) in those who continued to be negative.

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Median progression-free survival was 3.4 months (95% CI, 2.1 – 4.6), 16.8 months (95% CI, 6.9 – 26.8), and 15.3 months (95% CI, 1.1 – 29.6), respectively (P < .001).

Similar results were observed among patients treated with BRAF inhibitors like vemurafenib.


  1. Cao MG, Manzano  JL, Soriano V, et al. BRAF mutation analysis in cell free tumoral DNA (cfDNA) of melanoma patients: results from the prospective study GEM1304 (Spanish Melanoma Group). Poster presentation at: AACR Annual Meeting 2016; April 16-20, 2016; New Orleans, LA.