Background: Immune checkpoint inhibitors (ICIs) targeting PD-(L)1 are standard front-line therapy for advanced non-small cell lung cancer (NSCLC). Molecularly targeted tyrosine kinase inhibitors (TKIs) are standard of care for subsets of oncogene-driven NSCLC. Published literature suggests the possibility of increased toxicity in patients who receive ICIs followed by EGFR or ALK TKI treatment. However, the toxicity profile in patients who receive ICIs followed by TKIs with other genomic targets has not been well described. Methods: Marketing applications for TKIs in patients with NSCLC submitted to the Office of Oncologic Diseases between Jan 2019 to Dec 2022 were reviewed. Datasets were analyzed for demographics, treatment-emergent adverse events (TEAE), and prior anti-cancer therapies for TKI-treated patients in the primary efficacy population. Drug classes for which < 5% of patients received prior ICI were excluded. Grade 3-4 TEAE, serious adverse events (SAE), discontinuation TEAE and TEAE of interest (hepatotoxicity, rash, and interstitial lung disease [ILD]) were summarized. Results: 9 applications were identified and 2 were excluded. The remaining applications involved TKIs targeting EGFR exon 20 insertion, KRAS G12C, MET exon 14 skipping, and RET fusion alterations. Analyses included 867 patients; 61% received prior ICI therapy. Patient characteristics and results of analyses are presented in the table. In our pooled analysis, the incidence of Grade 3-4 AEs, SAEs, and hepatotoxicity were slightly higher in the prior ICI group, while the incidence of discontinuation TEAE, ILD, and rash were similar between groups. Analysis for hepatotoxicity was limited to reported AEs (did not include analysis of laboratory data). Review of toxicity data across individual drug classes did not show major differences compared to the overall results. Conclusions: Our analysis of safety data for newer TKIs with varied genomic targets does not appear to show excessive toxicity in patients with NSCLC who received prior ICI compared to those who did not. In future clinical trials evaluating TKIs in this population, inclusion of patients who have received prior ICI therapy should be considered when appropriate.