WCLC 2025 - Posters & ePosters-P3.18.54 Increasing the Dosing Interval of Osimertinib in Patients With EGFR-Mutated Advanced NSCLC (OSI-SAVE Study Design)

P3.18.54 Increasing the Dosing Interval of Osimertinib in Patients With EGFR-Mutated Advanced NSCLC (OSI-SAVE Study Design)

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This document presents the protocol for the OSI-SAVE trial, an international randomized controlled non-inferiority study evaluating the efficacy and safety of extending the dosing interval of osimertinib in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). Osimertinib, a standard first-line therapy, is typically given at 80 mg once daily (QD) but is associated with high rates (98%) of adverse events and severe toxicity in 34% of patients. Given osimertinib's long half-life (~44 hours) and consistent drug exposure (AUC) at 40 mg QD, the study investigates whether administering 80 mg every other day (QOD) can maintain efficacy while reducing toxicity and treatment costs.<br /><br />The primary endpoint is progression-free survival (PFS), with secondary endpoints including overall survival (OS), patient-reported toxicity (using PRO-CTCAE), quality of life (EQ-5D), incidence of CNS metastases, and an economic assessment. Exploratory analyses include pharmacokinetics, pharmacogenetics, and circulating tumor DNA (ctDNA). This is the first large-scale trial to assess the safety and efficacy of extended-interval osimertinib dosing.<br /><br />Prior studies have demonstrated osimertinib’s robust efficacy at standard doses, with objective response rates ranging from 59%-87% depending on dosing and patient population. The proposed 80 mg QOD regimen could potentially reduce toxicity without compromising effectiveness due to steady drug levels achieved with intermittent dosing, potentially lowering monthly treatment costs (approximately €3,000/patient in Europe). <br /><br />The study is conducted by multiple European oncology centers, with enrollment beginning in 2026, interim analysis planned for 2028, and final study completion targeted for 2032. Positive results could lead to establishing 80 mg every other day as a new standard-of-care dosing regimen, optimizing patient outcomes while mitigating adverse effects and healthcare expenditures.

Asset Subtitle

Maaike van den Bos

Meta Tag

Speaker Maaike van den Bos

Topic Clinical Trials in Progress

Keywords

OSI-SAVE trial

osimertinib

non-small cell lung cancer

EGFR mutation

extended dosing interval

progression-free survival

toxicity reduction

pharmacokinetics

quality of life

cost-effectiveness