BRAF+ melanoma
What makes it different, makes it vulnerable

Prognosis of BRAF+ melanoma

BRAF mutation may be associated with a worse prognosis versus wild-type BRAF1-6

Multiple studies have examined the relationship between BRAF mutation and overall survival in patients with stage III and stage IV disease.1-6 In a prospective study of 197 metastatic melanoma patients, overall survival was significantly decreased in those with a BRAF mutation who had not received treatment compared with those patients with wild-type BRAF (see figure below).1

Prospective analysis of 197 untreated patients by BRAF mutation1

Adapted with permission from: Long GV et al. J Clin Oncol. 2011;29(10):1239-46.

 

In a study of patients with resected stage IIB, IIC, or III melanoma, patients with BRAF mutation–positive disease showed a poorer overall survival than patients with wild-type BRAF (see figure below).7

Prospective analysis of overall survival by BRAF status for the observation arm patients7

Adapted from Corrie PG, et al. Ann Oncol. 2018;29(8):1843-52. Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

 

Meta-analysis and systematic review of advanced and metastatic melanoma by BRAF mutation8

A meta-analysis of 6 clinical studies of checkpoint inhibitors was conducted to evaluate the survival in different clinical and molecular subgroups based on PD-1 gene expression status, BRAF gene mutation status, serum LDH level, and demographic factors. The 6 studies included CheckMate 037, CheckMate 066, CheckMate 067, CheckMate 069, KEYNOTE-006, and KEYNOTE-002. Looking specifically at the BRAF gene mutation subgroups, a benefit in overall survival was observed in the BRAF wild-type subgroup (HR, 0.65 [95% CI, 0.49-0.85]; P = .002). However, a significant difference was not observed in the BRAF-mutant subgroup (HR, 1.10 [95% CI, 0.74-1.62]; P = .64). This study showed that in patients with BRAF-mutant melanoma, checkpoint inhibitors did not have a significant impact on overall survival.

Recognising the difference in survival in patients with and without BRAF mutation suggests the activating mutation may make a patient more vulnerable to a worse prognosis. Thus, this highlights the importance of identifying BRAF mutations early in the disease to help inform treatment decisions.

 

  1. Long GV, et al. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol. 2011;29(10):1239-46.
  2. Jakob JA, et al. NRAS mutation status is an independent prognostic factor in metastatic melanoma. Cancer. 2012;118(16):4014-23.
  3. Ugurel S, et al. B-RAF and N-RAS mutations are preserved during short time in vitro propagation and differentially impact prognosis. PLoS ONE. 2007;2(2):e236.
  4. Thomas NE, et al. Association between NRAS and BRAF mutational status and melanoma-specific survival among patients with higher-risk primary melanoma. JAMA Oncol. 2015;1(3):359-68.
  5. Hugdahl E, et al. BRAF-V600E expression in primary nodular melanoma is associated with aggressive tumour features and reduced survival. Br J Cancer. 2016;114(7):801-8.
  6. Jacquelot N, et al. Immunophenotyping of stage III melanoma reveals parameters associated with patient prognosis. J Invest Dermatol. 2016;136(5):994-1001.
  7. Corrie P, et al; AVAST-M Investigators. Adjuvant bevacizumab as treatment for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial. Ann Oncol. 2018;29(8):1843-52.
  8. Badami S, et al. Clinical and molecular characteristics associated with survival in advanced melanoma treated with checkpoint inhibitors. J Oncol. 2018:6279871.