MO2-16-2Irreversible severe cardiotoxicities except for QTc interval prolongation associated with Osimertinib

Background QTc interval prolongation is a known and warning cardiotoxicity associated with Osimertinib. The final summary on the safety profile of Osimertinib (AstraZeneca plc) reports that severe cardiotoxicities except for QTc interval prolongation are 0.8% (29/3578 patients) and alerts us to such adverse events. Here, we report irreversible severe cardiotoxicities associated with Osimertinib except for QTc interval prolongation. Methods We reviewed the medical records of EGFR-mutated Non-Small Cell Lung cancer patients who were treated with Osimertinib at Osaka International Cancer Institute between March 2016 and January 2019. We checked cardiotoxicities associated with Osimertinib based on the medical records. Results We enrolled 123 patients treated with Osimertinib into this study. The median age was 69 (range: 33-86) years. Of 123 patients, 40 (32.5%) were male, all cases except one were adenocarcinoma, EGFR mutation profile was Ex. 19 del/L858R/de novo T790M/others(G719S, L861Q); 62 (50.4%)/56 (45.5%)/3/2. Osimertinib treatment line was 1st; 23 (18.7%), 2nd; 30 (24.4%), 3rd; 18 (14.6%), ≥4th; 41 (33.3%), 11 pts; switching from other EGFR-TKI during 1st line. Severe cardiotoxicities (CTC-AE Gr.3≥) were observed in 5 pts (4.1%); acute myocardinal infarction (1), irreversible congestive heart failure due to systolic dysfunction (1), exacerbation of tricupid regurgitation (1), decreasing ejection fraction (EF) (2). Histopathological analysis of a myocardial biopsy from one patient with decreased EF (Gr.2) revealed inflammatory cells infiltration into cardiomyocytes. Conclusion We experienced severe cardiotoxicities associated with Osimertinib at a higher frequency (4.1%) than reported before. Considering some patients were forced to quit their chemotherapy due to severe cardiotoxicities. We should pay attention to not only QTc interval prolongation but also other cardiotoxicities in administrating Osimertinib in the clinical setting.