Pharmacological considerations for prescribing of small molecule inhibitors in patients with non-small cell lung...

Small molecule inhibitors (SMIs) have become the cornerstone of treatment for patients with oncogene-driven non-small cell lung cancer (NSCLC), substantially improving clinical outcomes. Over the past decade, numerous agents targeting distinct oncogenic drives have been developed, each exhibiting unique pharmacokinetic and pharmacodynamic profiles that complicate clinical prescribing. This review highlights principal drug-interactions affecting SMI exposure, including concomitant food intake, gastric acid suppressants, modulators of cytochrome P450 (CYP) enzymes and drug transporters. Awareness of these factors may help prevent early treatment failure or severe adverse events due to under- or overexposure. Finally, the most prevalent and clinically relevant toxicities are discussed, including corrected QT interval (QTc) prolongation, pneumonitis, mucositis, weight gain, pyrexia, and ocular-, hepatic-, and neuro-toxicity. In line with recommendations from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), this review which is based on extensive search of the scientific literature provides evidence-based practical guidance for prescribing SMIs in clinical practice.