Meeting with triumph and disaster: Osimertinib in T790M-unknown CNS progression in EGFR-mutated non-small cell lung cancer:

Introduction:Treatment paradigms for EGFR-mutated non-small cell lung cancer (NSCLC) have successfully evolved since the introduction of osimertinib. The detection of EGFR T790M mutation in plasma or tumor samples obtained at disease progression to first-/second-generation EGFR inhibitors is mandatory for osimertinib prescription. Nevertheless, pharmacokinetics properties of osimertinib guarantee its usefulness in central nervous system (CNS) disease even in the case of T790M-negative or unknown status.Patients and methods:In this brief report, we share the clinical histories of two patients with CNS-preeminent progression under first-/second-generation EGFR inhibitors in which it was not possible to document the presence of T790M resistance mutation.Results:Patient outcomes diverged dramatically due to the differential availability of off-label osimertinib.Conclusions:Waiting for the novel molecule to be approved and licensed in first-line treatment, our report of hope and frustration is intended to stre...