Background: First generation EGFR TKIs are well tolerated with chemotherapy (chemo), and have evidence of improved efficacy in EGFR-mutant NSCLC. Osimertinib (osi) is a 3rd-generation EGFR TKI with improved T790M and CNS activity. Safety and outcome data combining osi and concurrent chemo are limited. Methods: EGFR-mutant pts who received osi with chemo between 12/2015 and 8/2018 were retrospectively identified at two institutions. Pt demographics, toxicities and outcomes were collected by chart review. Results: 35 pts received osi + chemo, 29/35 pts had CNS mets. 16/35 had > = one prior chemo and/or immunotherapy, 34/35 previously received a 1^st/2nd gen EGFR TKI (25/35 T790M+ at progression), and all 35 had prior progression on osi. 47 osi + chemo regimens were abstracted: carboplatin/pemetrexed+/-bevacizumab (n = 17), cisplatin/pem (1), carbo/taxane (2), pem+/-bev (7), taxane (7), gemcitabine (8), irinotecan (3), vinorelbine (2); 32/35 pts had platinum. Osi was dosed at 80 mg QD (32), 160 mg QD (2), or 80mg QOD (1). Toxicities (table) occasionally led to treatment delay (n = 5), osi dose-reduction (2) and discontinuation (3). Median overall survival (mOS) from metastatic diagnosis was 48.4 mo (95% CI 30.7-NR); mOS from first osi was 19.6 mo (95% CI 16.1-32.6). Median duration of treatment (mDOT) for first regimen of chemo + osi was 5.3 mo (95% CI 4.1-9.5); stratifying by chemo, mDOT for platinum doublet + osi was 6.1 mo (95% CI 4.7-NR) and mDOT for osi + single agent was 3.2 mo (95% CI 2.4-5.3). In the 29 pts with brain mets receiving their first regimen of osi + chemo, 6 had CNS progression but only 2 required radiation at progression. Conclusions: Osimertinib is tolerable in combination with many standard chemo regimens for EGFR-mutant NSCLC. mDOT for platinum doublet and single agent are similar to historical controls, but CNS disease control appears better than expected for chemotherapy alone. Adding chemotherapy at the time of progression on osimertinib may be considered for selected pts, particularly those with known CNS mets.