Lyudmila Bazhenova, MD of the University of California, San Diego discusses Metastatic EGFR mutation + Osimertinib in NSCLC first line, second line, third line setting. Dr. Bazhenova chooses osimertinib first line for patients who were just newly diagnosed with EGFR mutant Stage 4 non-small cell lung cancer. However, since osimertinib in the first line setting is not yet FDA approved, using osimertinib still depends on the insurance company. Though its already in the NCCN guidelines, but if the insurance company doesnt approve osimertinib, then the first generation EGFR TKIs of their choice will be given and biopsy upon progression. In this case, osimertinib will be given in second line.
So, for the typical sequence of first generation, erlotinib with gefitinib, then upon progression the discovery of T790M, osimertinib will be given second line. If after EGFR TKI progression, T790M is negative then, platinum-based doublet will be used.
If osimertinib is used first-line and the patient progressed, biopsy is recommendable to look for the resistance mechanism of the patient. Small-cell transformation has been described in osimertinib resistance. Other resistance mechanism for osimertinib that has been described includes C779S mutation, which predicts resistance to osimertinib. For post-osimertinib progression, the de facto standard should be chemotherapy, platinum-based doublet of your choice, plus or minus bevacizumab. If you find other resistance mechanism in the clinical trial, checking the clinical trial will be important as well.