Beyond the standard 80 mg: Exposure-guided and equity-oriented precision dosing of Osimertinib in EGFR-mutant NSCLC

Background Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has become foundational therapy across the EGFR-mutant non-small cell lung cancer (NSCLC) continuum, including first-line metastatic disease, unresectable stage III consolidation, and adjuvant therapy after resection. Yet routine clinical use still assumes a uniform fixed dose of 80 mg once daily, despite broad pharmacokinetic (PK) variability, substantial toxicity-mediated dose interruptions, and persistent uncertainty about an exposure-defined therapeutic window—particularly in India, where competing risks, polypharmacy, and affordability pressures shape adherence and persistence. Objective This narrative review advances the thesis that Osimertinib should be reframed not only as a fixed-dose targeted drug but as a compelling candidate for exposure-guided precision dosing—leveraging therapeutic drug monitoring (TDM), exposure–response evidence, and pharmacometric modeling to improve tolerability, continuity, and equity of access. Evidence synthesis Clinical development and regulatory labeling provide convergent signals of an efficacy plateau across a wide dose range and stronger concentration dependance for select toxicities (rash, diarrhea, QTc prolongation), consistent with the broader “flat efficacy–steep toxicity” pattern observed with many targeted agents. Population PK (PopPK) analyses and real-world cohorts further highlight interpatient exposure spread, proposed toxicity thresholds (notably a candidate toxic limit of 259 ng/mL, derived from a single real-world cohort and requiring external validation), and operational feasibility of plasma- or microsampling-based assays. However, existing datasets remain heterogeneous, and no globally accepted therapeutic range exists. Conclusions Osimertinib precision dosing is an emerging, plausible, and equity-relevant paradigm—especially in India and other resource-constrained settings—but requires prospective, locally anchored therapeutic window studies, pragmatic TDM workflows, and model-informed dose adaptation trials before routine implementation. Pending such evidence, exposure-guided dosing should be regarded as investigational rather than standard care.