Longitudinal plasma osimertinib concentrations during treatment in patients with EGFR-mutant NSCLC: a prospective real-world study

Abstract Background Osimertinib is used across treatment settings for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Dose reduction is sometimes required for tolerability; however, efficacy is often maintained. We evaluated longitudinal plasma trough concentrations (C_trough) in patients receiving osimertinib. Methods Patients with EGFR-mutant NSCLC receiving osimertinib who provided informed consent for a prospective observational study between March 2022 and May 2024 were included. Blood samples were obtained at each visit, and plasma concentrations were quantified using a validated assay. Among the patients initiated on 80 mg once daily, the association between the initial C_trough and subsequent dose reduction for toxicity was evaluated. Clinical correlates of exposure were assessed by relating the dose-normalized concentration (C/D ratio) to baseline characteristics. Results Twenty-five patients were evaluated. Patients requiring dose reduction (n = 6) had a higher initial C_trough on days 6–14 than did those who did not (median, 466.5 versus 224 ng/mL; P = .0094). Among 15 patients treated ≥18 months, long-term therapy was sustained across a wide concentration range. Of the 70 long-term samples, 96% were ≤ 268.5 ng/mL. The C/D ratio was higher in females than males, inversely correlated with body weight and body surface area, and positively correlated with the neutrophil-to-lymphocyte ratio. Conclusions Higher early osimertinib exposure was observed in patients who subsequently required dose reduction because of toxicity. Plasma concentration measurement may provide complementary information on individual drug exposure when assessing tolerability. Long-term treatment was observed across a broad concentration range following dose modification.