Reduced frequency dosing of osimertinib in EGFR-mutant non-small cell lung carcinoma: Real world data

Abstract

Abstract Introduction Osimertinib has better efficacy than first generation EGFR-directed TKIs with similar safety profile. However, osimertinib is not affordable for most in developing nations. Moreover, minimum biologically effective dose of osimertinib may be less than approved, given uncertainty surrounding dose determination strategy for targeted agents Materials and Methods This was retrospective observational multicentric study aimed to describe the objective response rate(ORR), disease control rate(DCR), progression free survival(PFS), overall survival(OS), and toxicity of osimertinib 80 mg orally administered less frequently than daily (ranging from alternate day to once weekly) in patients with EGFR-mutated non-small cell lung cancer. Results Between January 2021 and August 2023, we enrolled 22patients. Six received osimertinib 80mg once weekly, nine received 80mg every three days, and seven received 80mg alternate days. Responses included 0 complete responses, 7(31.8%) partial responses, 9(40.9%) stable diseases, and 5(22.7%) progressive disease. ORR was 31.8%, and DCR was 72.7%. Median PFS was 9.2months (95% confidence interval[CI] 2.9–15.7), and median OS was 17.8months (95%CI, 3.2–32.6). In patients who received reduced frequency osimertinib in the second line and beyond, the ORR was 29.4%, DCR was 70.5%, median PFS was 5.9months (95%CI, 1.1–10.6) and median OS was 17.6months (95%CI, 2.9–32.2). Grade- 3 and higher toxicities were noted in 8(36.3%) patients. Conclusion Less frequent dosing of osimertinib may be valid treatment option especially in second line and beyond in patients who cannot afford full dose osimertinib. This may provide additional treatment option with similar toxicity profile as standard dose osimertinib.