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Aim: Sunitinib is an oral tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST). Because of the large interpatient pharmacokinetic variability and established exposure‐response and exposure‐toxicity relationships in clinical trial patients, therapeutic drug monitoring (TDM) seems promising for optimizing sunitinib exposure. We aimed to investigate the relationship between sunitinib exposure and treatment outcome in a real‐world patient cohort. Methods: We performed a retrospective observational cohort study in 53 patients with metastatic RCC and 18 patients with metastatic GIST treated with sunitinib and receiving TDM‐guided dosing. Time on treatment – as a surrogate for progression‐free survival – in patients who achieved adequate sunitinib exposure was compared with patients who did not. Additionaly, the median sunitinib exposure was compared in patients with or without sunitinib‐induced toxicity leading to dose reduction. Results: The median time on treatment in patients with RCC who achieved adequate sunitinib exposure (n = 39) was 32 weeks, compared to 15 weeks in patients who did not achieve adequate sunitinib exposure (n = 12) (P = 0.244). In 29 patients (41%) with toxicity leading to dose reduction, sunitinib sum plasma trough concentration (Ctrough) until dose reduction was significantly higher compared to patients without toxicity leading to dose reduction (median 60 ng/mL vs 44 ng/mL; P < 0.001) and reduced to comparable levels after dose reduction (44 ng/mL; P = 0.488). Conclusion: In our real‐world patient cohort, patients with sunitinib‐induced toxicity requiring dose reduction had significantly higher sunitinib exposure compared to patients without toxicity. The threshold for toxicity, however, was lower compared to that previously described in clinical trials. [ABSTRACT FROM AUTHOR]

Tyrosine kinase inhibitors (TKIs) are anti‐cancer drugs that target tyrosine kinases, enzymes that are involved in multiple cellular processes. Currently, multiple oral TKIs have been introduced in the treatment of solid tumours, all administered in a fixed dose, although large interpatient pharmacokinetic (PK) variability is described. For imatinib, sunitinib and pazopanib exposure‐treatment outcome (efficacy and toxicity) relationships have been established and therapeutic windows have been defined, therefore dose optimization based on the measured blood concentration, called therapeutic drug monitoring (TDM), can be valuable in increasing efficacy and reducing the toxicity of these drugs. In this review, an overview of the current knowledge on TDM guided individualized dosing of imatinib, sunitinib and pazopanib for the treatment of solid tumours is presented. We summarize preclinical and clinical data that have defined thresholds for efficacy and toxicity. Furthermore, PK models and factors that influence the PK of these drugs which partly explain the interpatient PK variability are summarized. Finally, pharmacological interventions that have been performed to optimize plasma concentrations are described. Based on current literature, we advise which methods should be used to optimize exposure to imatinib, sunitinib and pazopanib. [ABSTRACT FROM AUTHOR]