Correct!
4. 1 and 3

In this case it was not entirely clear how to proceed. The new lung lesion was treated with stereotactic body radiation, but erlotinib was continued since the patient was doing reasonably well, and at the time, no targeted therapies were available for the T790M mutation. However, only two months later the original cancer was seen to progress. At that time osimertinib, an irreversible EGFR tyrosine kinase inhibitor that is selective for T790M mutations and has activity in the central nervous system, became available. Osimertinib has been shown to be superior to platinum doublet chemotherapy as a second-line therapy for advanced NSCLC harboring exon T790M following the failure of first or second-generation EGFR-TKI (4).  She was begun on osimertinib and has had only mild fatigue as a side effect of the new therapy. Six months later her thoracic scan is devoid of any evidence of parenchymal lung tumor. Her CNS remains clear, and the bone changes are stable as well.

This case illustrates that lung cancer pathobiology can change with time and tumors initially sensitive to a therapy can develop resistance. However, therapy guided by rebiopsy and genetic analysis of the tumor can yield dramatic results.

References

  1. Keedy VL, Temin S, Somerfield MR, et al. American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) Mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. J Clin Oncol. 2011 May 20;29(15):2121-7. [CrossRef] [PubMed]
  2. Markman M. Genetics of non-small cell lung cancer. Medscape. June 8, 2017. Available at: https://emedicine.medscape.com/article/1689988-overview#a1 (accessed 2/12/18).
  3. Wu YL, Zhou C, Liam CK, et al. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 2015 Sep;26(9):1883-9. [CrossRef] [PubMed]
  4. Okuma Y, Hosomi Y. Osimertinib for advanced non-small cell lung cancer harboring EGFR mutation exon 20 T790M, acquired resistant mutation for first- or second-generation EGFR-TKI. J Thorac Dis. 2017 Mar; 9(3):470-3. [CrossRef] [PubMed]

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