• NSCLC (Non Small Cell Lung Cancer)
  • Commonly related to smoking or exposures but can see it in non-smokers (adenocarcinoma) with de-novo mutations
  • Staging --> PET Scan, CT Chest, MRI Brain given potential to metastasize to CNS
  • Stage IV has poor prognosis and median survival of less than 1 year
  • Survival is slightly better if you have a driver mutation
  
  

  Posted 01/25/17 09:20:25 AM by Ying Liu

• Driver Mutations to Check for in Lung Cancer
  • EGFR 
    • Epidermal growth factor receptors (EGFR) are tyrosine kinases that control growth. Mutations in these receptors that cause them to be constitutively active can lead to cancer
    • Mutations in EGFR are seen in 15% of NSCLC adenocarcinoma and are even more frequent in women and non-smokers
    • Erlotinib in an EGFR TKI and is associated with improved PFS but not OS compared with chemotherapy 
    • Resistance to these EGFR TKI’s is common and can lead to progression of disease
    • Toxicities include rash, diarrhea and uncommonly interstitial pneumonitis
  • ALK
    • Anaplastic lymphoma kinase (ALK) rearrangements result in oncogenes that encode a constitutively active kinase
    • This rearrangement is seen in 4-7% of NSCLC but may be more common in non-smokers, those with adenocarcinoma and those without an EGFR mutation
    • Patients are usually younger
    • Crizotinib can be used as initial therapy or can be given following chemotherapy regardless of progression
    • Phase III trials showed improved PFS and quality of life but no differences in OS as compared with chemotherapy
    • May also have moderate activity against brain metastases
    • Generally well tolerated but toxicities include GI sides effects, LFT abnormalities, pneumonitis, cardiac toxicity (bradycardia and QTc prolongation), drug interactions with CYP3A4 inhibitors, and hypersensitivity reactions
  
  
  
  

  Posted 01/25/17 09:24:14 AM by Ying Liu

• For further reading...

  N Engl J Med 2013; 368:2385-2394
  
  

  Posted 01/25/17 09:25:06 AM by Ying Liu

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