Osimertinib rechallenge in advanced EGFR non-small cell lung cancer patients

e21196 Background: Treatment after front line osimertinib (osi) for epidermal growth factor receptor (EGFR) mutated advanced non-small cell lung cancer (NSCLC) remains a clinical challenge. Interval chemotherapy after osi may eradicate clones responsible for EGFR tyrosine kinase (TKI) resistance, which may re-sensitize the tumor to EGFR inhibition. We describe outcomes of metastatic EGFR NSCLC patients who undergo osi rechallenge. Methods: NSCLC patients with confirmed EGFR mutation were retrospectively reviewed from a single institutional database from 1/2010-12/2022. We identified patients who received osi after interval therapy following initial osi progression. Patient characteristics and tumor type were collected via chart review. Response was determined using RECIST 1.1. Results: Seventeen patients with osi rechallenge after initial progression were identified. Median age at time of osi rechallenge was 62 yrs (range 42-73). Patients were predominantly female (n = 11, 65%), white (n = 9, 53%) and Asian (n = 8, 47%), never smokers (n = 13, 77%). Patients had either del19 mutation (n = 10, 59%) or L858R mutation (n = 7, 41%). Twelve patients (71%) received a 1 st or 2 nd generation EGFR TKI (erlotinib n = 10, afatinib n = 2) prior to initial osi; eight patients (47%) had confirmed T790M mutation. Eight patients (47%) had CNS metastases prior to osi rechallenge. Twelve patients (71%) had ECOG 0-1 at time of rechallenge. Patients had a median of 4 (range 2-5) lines of therapy prior to osi rechallenge. Median time between initial osi discontinuation and osi rechallenge was 13.8 months (range 3.2-50.7). In the interim, 17 patients (100%) received chemotherapy, 2 (12%) received immunotherapy monotherapy, 3 (18%) received antibody drug conjugate, and 1 (6%) received TKI. Sixteen patients had follow-up restaging CT scans; 1 died before restaging imaging was obtained. Two patients achieved partial response (PR) (13%), and 6 patients had stable disease (SD) as the best response (38%). Median duration of initial osi was 13.9 months (range 1.9-26.4), and median duration of osi rechallenge was 3.6 months (range 1.0-10.3). Patients who had PR/SD were on osi for 7.5 months (range 2.7-10.3). Ten (59%) patients received osi rechallenge for at least 3 months duration, and 6 (35%) received osi rechallenge for at least 6 months duration. Conclusions: Osi rechallenge is a potential option for advanced EGFR NSCLC patients to obtain disease control at later lines of therapy. Further research is needed to characterize mechanisms of targeted therapy resistance and better select patients who can benefit from EGFR TKI re-exposure.