Abstract 1248P
Background
Whilst tyrosine-kinase inhibitors (TKIs) have revolutionised the treatment of non-small cell lung cancer (NSCLC), some are associated with cardiotoxicity. With eligibility criteria not as restrictive as clinical trials, real-world data is needed for establishing safety. This study aims to compare the development of cardiotoxicity in the real-world setting to those reported in clinical trials. We investigated whether patients who developed cardiotoxicity induced by osimertinib and crizotinib would have met respective clinical trials inclusion criteria.
Methods
Retrospective data with inclusion criteria of having received at least one dose of a UK approved TKI at the Royal Marsden. This was over a two-year timeframe (2017-2019), providing a meaningful sample size. Cardiotoxicity was defined as per CTCAE V.5. A literature review was conducted on PubMed, Science Direct and ClinicalTrials.gov to identify published trials on osimertinib and crizotinib. Patients who developed cardiotoxicity associated with osimertinib and crizotinib in our real-world study were compared to trials eligibility criteria. Variations of cardiotoxicity incidence among the real-world study and clinical trials were investigated. FLAURA, AURA3, PROFILE1007 and PROFILE1014 were the trials included for analysis.
Results
18% (n=37/206) of patients developed cardiotoxicity. Osimertinib and crizotinib were responsible for n=7/33, 21.2%, and n=7/22, 31.8% of cardiotoxicities, respectively. None of the patients would have been eligible to participate in FLAURA and PROFILE1014 trials whereas n=4/7 and n=5/7 patients would have been eligible to enrol in AURA3 and PROFILE1007. Exclusion reasons were prior treatment with other anti-cancer agents and the presence of other diseases. Cardiotoxicity incidence in the real-world study is consistent with FLAURA (20%) (OR=1.04, P=0.09), but higher than AURA3 (9.8%) (OR=2.5, P=0.07), PROFILE1007 (4.1%) (OR=11, P<0.001) and PROFILE1014 (2.3%) (OR=19.5, P<0.001).
Conclusions
Although clinical trials give the drug a licence, real-world studies are needed to show the true safety profile and the real risk of cardiotoxicity. Further investigation is required into risk factors contributing to the development of cardiotoxicity.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.