- Acquired resistance mechanisms to osimertinib can be EGFR dependent or independent.
- First- and fourth-generation EGFR-TKIs are able to overcome EGFR-dependent resistance.
- MET and MEK inhibitors may overcome EGFR-independent resistance.
- Anti-HER/MET novel monoclonal antibody seems effective across multiple resistance mechanisms.
- Carboplatin/paclitaxel ± bevacizumab/atezolizumab represents a feasible option in ‘fit’ patients progressing on osimertinib.