Neoadjuvant BRAF-targeted therapy in regionally advanced and oligometastatic melanoma

Pigment Cell Melanoma Res. 2020 Jan;33(1):86-95. doi: 10.1111/pcmr.12813. Epub 2019 Sep 12.

Abstract

Current management of locoregional and oligometastatic melanoma is typically with surgery; however, some patients are unable to undergo resection due to location/size of their tumors and/or the anticipated morbidity of the surgery. While there are currently no established guidelines for neoadjuvant therapy in melanoma, neoadjuvant BRAF-targeted therapy may make resection more feasible. A retrospective analysis was conducted of 23 patients with BRAFV600-mutant, stage III/IV melanoma treated with BRAF-targeted therapy prior to surgery, with no adjuvant treatment. Surgical specimens, preoperative imaging, and clinical outcomes were evaluated. Results: Ten of 23 patients (44%) attained a pathologic complete response (pCR), with no correlation between RECIST response based on preoperative imaging and pathologic response. After a median of 43-month follow-up, only 1 patient (10%) with a pCR recurred, while 8 of 13 (62%) patients without a pCR recurred. Patients with a pCR had significantly improved relapse-free (RFS) and overall survival (OS) compared to patients with residual tumor. Neoadjuvant BRAF-targeted therapy is associated with a high pCR rate in patients with stage III-IV melanoma, which may correlate with improved RFS and OS.

Keywords: BRAF-targeted therapy; melanoma; neoadjuvant therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Disease-Free Survival
  • Female
  • Humans
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use
  • Male
  • Melanoma / diagnostic imaging
  • Melanoma / pathology*
  • Melanoma / therapy*
  • Middle Aged
  • Molecular Targeted Therapy*
  • Neoadjuvant Therapy*
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Oximes / pharmacology
  • Oximes / therapeutic use
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / metabolism
  • Pyridones / pharmacology
  • Pyridones / therapeutic use
  • Pyrimidinones / pharmacology
  • Pyrimidinones / therapeutic use
  • Treatment Outcome

Substances

  • Imidazoles
  • Oximes
  • Pyridones
  • Pyrimidinones
  • trametinib
  • Proto-Oncogene Proteins B-raf
  • dabrafenib