Brief Report: Risk of Recurrent Interstitial Lung Disease From Osimertinib Versus Erlotinib Rechallenge After Symptomatic Osimertinib-Induced Interstitial Lung Disease

IntroductionInterstitial drug disease (ILD) is the most frequent cause of drug-related mortality from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI).Yet, for patients with symptomatic osimertinib-induced ILD, the risk of recurrent ILD associated with EGFR TKI rechallenge, either with osimertinib or another TKI, such as erlotinib, is unclear. MethodsRetrospective study of 913 patients who received osimertinib treatment for EGFRmutation positive non-small cell lung cancer (NSCLC).Clinical characteristics, ILD treatment history, and subsequent anticancer therapy of patients with symptomatic osimertinib-induced ILD were collated.The primary endpoint was to compare the incidence of recurrent ILD with osimertinib versus erlotinib rechallenge. ResultsThirty-five out of 913 patients (3.8%) had symptomatic osimertinib-induced ILD, of which 12 (34%), 15 (43%) and 8 (23%) had grade 2, 3 to 4, and 5 ILD respectively.Upon ILD recovery, seventeen patients had EGFR TKI rechallenge with 8 received osimertinib and 9 received erlotinib.The risk of recurrent ILD was higher with osimertinib rechallenge than erlotinib (p=0.0498).5 out of 8 (63%) developed recurrent ILD on osimertinib rechallenge, including 3 patients with fatal outcomes.In contrast, only 1 out of 9 patients (11%) treated with erlotinib had recurrent ILD.Median time to second ILD occurrence was 4.7 weeks (range 0.7-12).Median time-to-treatment failure of patients with erlotinib rechallenge was 13.2 months (95% CI 8.6-15.0). J o u r n a l P r e -p r o o f ConclusionsThe risk of recurrent ILD was significantly higher with osimertinib rechallenge than erlotinib.Osimertinib rechallenge should be avoided while erlotinib may be considered in patients with symptomatic osimertinib-induced ILD.