Tumor flare after start of RAF inhibition in KRAS mutated NSCLC: a case report

Lung Cancer. 2015 Feb;87(2):201-3. doi: 10.1016/j.lungcan.2014.11.014. Epub 2014 Nov 29.


Here we describe a case of striking tumor flare after start of treatment with sorafenib and metformin as part of a phase II clinical trial. Previous reports have described a paradoxal activation of the MAPK pathway after treatment with a weak RAF inhibitor. This mechanism is based on inhibition of a negative feedback loop to upstream effectors of RAF and subsequently increased stimulation of the RAS-RAF-MEK-ERK (MAPK) pathway. We suggest that sorafenib may contribute to tumor progression through this mechanism and clinicians should be aware of this phenomenon when treating NSCLC patients with sorafenib.

Keywords: KRAS mutation; Non-small cell lung cancer; Paradoxal activation; RAF inhibitor; Sorafenib; Tumor flare.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Disease Progression
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Mutation*
  • Neoplasm Staging
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / metabolism
  • Signal Transduction / drug effects
  • Tomography, X-Ray Computed
  • Tumor Burden
  • ras Proteins / genetics*
  • ras Proteins / metabolism


  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins B-raf
  • Mitogen-Activated Protein Kinases
  • ras Proteins