Real-World Study of EGFR-TKI Rechallenge With Another TKI After First-Line Osimertinib Discontinuation in Patients With EGFR-Mutated Non-Small Cell Lung Cancer: A Subset Analysis of the Reiwa Study.

introductionFirst-line osimertinib is widely used to treat patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancers (NSCLC). In clinical practice, rechallenge therapy with another EGFR-tyrosine kinase inhibitor (TKI) is often performed after first-line TKI discontinuation owing to resistance or toxicity; however, the efficacy and toxicity of EGFR-TKI rechallenge after first-line osimertinib have not been adequately investigated. This study aimed to examine the efficacy and safety of EGFR-TKI rechallenge with another TKI.

methodsThis multicenter prospective observational study enrolled patients with EGFR-mutated NSCLC who received first-line osimertinib and another EGFR-TKI as second- or third-line treatment between September 2018 and August 2020.

resultsFifty-three patients received rechallenge with another EGFR-TKI in the second-line (n = 38, 71.7%) or third-line (n = 15, 28.3%) setting. The primary reason for first-line osimertinib discontinuation was toxicity in 32 (60.4%, 17 patients with pneumonitis) and disease progression in 20 (37.7%) patients. The most common rechallenge EGFR-TKI was afatinib (n = 24, 45.3%), followed by gefitinib (n = 16, 30.2%) and erlotinib (n = 8, 15.1%). The real-world time to treatment failure (rwTTF) was 7.3 months. The rwTTF for the toxicity discontinuation and progressive disease discontinuation groups was 9.3 months and 5.1 months, respectively, (HR 1.61, p = 0.119). EGFR-TKI rechallenge was discontinued due to toxicity in nine patients (17.0%), but no patient developed pneumonitis.

conclusionEGFR-TKI rechallenge with another TKI is well tolerated in patients with EGFR-mutated NSCLC. Thus, it may be a useful treatment option after first-line osimertinib failure, especially after osimertinib discontinuation due to toxicity.