Risk Assessment of Neutropenia Based on Exposure Information Without Plasma Concentration Measurement in Pemetrexed–Platinum-Based Chemotherapy: A Modeling Approach Using Real-World Clinical Data

Background/Objectives: Pemetrexed–platinum chemotherapy is a key treatment option for non-squamous non-small cell lung cancer (NSCLC); however, its use is often limited by hematologic toxicity, particularly neutropenia. We aimed to develop a model-informed framework for assessing neutrophil dynamics using routinely available clinical data and pemetrexed exposure.

Methods

This real-world investigation included 86 patients with NSCLC who received pemetrexed–platinum chemotherapy for model development, and 83 patients who received the same chemotherapy plus pembrolizumab or bevacizumab for validation. We developed a nonlinear mixed-effects model to predict neutrophil dynamics during the first cycle following pemetrexed–platinum chemotherapy, using patient-specific clinical data collected before chemotherapy initiation and pemetrexed pharmacokinetic parameters derived from physiologically based pharmacokinetic (PBPK) modeling.