Pharmacokinetic boosting of osimertinib with cobicistat in patients with non-small cell lung cancer: The OSIBOOST trial

• DOI: 10.1016/j.lungcan.2022.07.012
• Publication Date: 2022-07-25T16:23:55Z
• Authors: Ard van Veelen; Judith Gulikers; Lizza E.L. Hendriks; Safiye Dursun; Juanita Ippel; Egbert F. Smit; Anne-Marie C. Din...; Robin van Geel; Sander Croes
• Keywords: Osimertinib; Cobicistat; Clinical endpoint

Exposure to osimertinib, a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for treatment of non-small cell lung cancer (NSCLC) and sensitizing EGFR mutation, can be substantially below average. We evaluated whether plasma levels could boosted by co-administration cobicistat, strong Cytochrome P450 3A-inhibitor.This was pharmacokinetic, proof-of-concept clinical trial (the OSIBOOST trial, NCT03858491). NSCLC-patients with osimertinib were eligible if their steady state trough concentration low (≤195 ng/mL). On day 1, the area under curve (AUC0-24,ss) its metabolite (AZ5104) calculated using limited sampling strategy (four samples). Cobicistat co-treatment (150 mg, once daily) started on 2. Between 22-26, second AUC determined. dose escalated still ≤ 195 ng/mL, in absence toxicity. Primary endpoint increase exposure, secondary continued during expanded access phase, follow-up (2-4 months) boosting effect.The mean baseline eleven enrolled patients 154 ng/mL. In all patients, cobicistat addition led an exposure. Mean total AUC0-24ss (AUC + AZ5104) 60%, (range 19%-192%). The effect consistent over time. No grade ≥ 2 toxicity observed.Pharmacokinetic NSCLC is feasible without increasing toxicity, although degree variable.