A UK multicentre experience of osimertinib related cardiovascular toxicity: real world patterns risk stratification and surveillance

Abstract

Background and Aims: Osimertinib (Osi), a third-generation oral tyrosine kinase inhibitor (TKI) is the mainstay in metastatic non-small cell lung cancer (NSCLC) with EGFR mutations. The FDA Adverse Events Reporting System (FAERS) in 2019 established four forms of Osi associated cancer therapy related - cardiovascular toxicity (CTR-CVT): venous thromboembolism (VTE), cancer therapy related cardiac dysfunction (CTRCD), QTc interval prolongation and atrial fibrillation (AF). The August 2022 European Society of Cardiology (ESC) Cardio-Oncology guidelines recommends all patients on Osi having a baseline/pre-treatment along with three monthly transthoracic echocardiograms (TTEs) as surveillance. We aimed to evaluate real-world patterns of CTR-CVT incidence as well as baseline and surveillance TTE utilisation for CV risk stratification of Osi patients pre-ESC guideline publication. Method(s): Metastatic NSCLC patients >=18 years at diagnosis, on Osi between August 2017 and May 2022 from 2 UK tertiary cancer centres were identified from electronic health records and included in our retrospective analysis. CTR-CVT was defined as new diagnoses of VTE, CTRCD, QTc prolongation and/or AF after commencing Osi. Result(s): 170 patients were identified (Table 1). The incidence of VTE, QTc prolongation, AF and CTRCD was 12.9%, 5.3%, 1.2% and 1.2% respectively. The mean duration between starting Osi and onset of CTR-CVT was 459.6 (416.4), 341 (220.1) days, 593.5 (249.6) and 130.5 (40.31) days for VTE, QTc prolongation, AF and CTRCD respectively. All instances of CTRCD were symptomatic. Only 33/170 (19.4%) patients had a baseline TTE and 5/170 (2.9%) had three-monthly surveillance TTEs. Conclusion(s): Compared to the FAERS database results, our multi centre experience yielded a lower incidence of new AF and CTRCD whereas QTc prolongation and VTE had higher incidence. However, interpretation of these results is limited by a small sample size and lack of a comparator group. The low uptake of baseline and surveillance TTE coupled with our CTRCD incidence albeit symptomatic suggests an oncological toxicity symptom guided cardiology practice. This might compromise baseline CV risk stratification as well as hinder early recognition of asymptomatic CTRCD and accordingly early cardio-protective interventions. As our service was analysed retrospectively before the 2022 ESC Cardio-Oncology guidelines, a re-evaluation to assess change in baseline and surveillance TTE utilisation is warranted and currently underway. Oncological engagement into baseline cardio-oncology practice, cost and labour effectiveness of cancer drug toxicity surveillance programmes are key considerations.