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The relationship between sunitinib exposure and both efficacy and toxicity in real-world patients with renal cell carcinoma and gastrointestinal stromal tumour.

Abstract：

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.

journal_name

Br J Clin Pharmacol

journal_title

British journal of clinical pharmacology

authors

Westerdijk K,Krens SD,van der Graaf WTA,Mulder SF,van Herpen CML,Smilde T,van Erp NP,Desar IME

doi

10.1111/bcp.14332

subject

Has Abstract

pub_date

2020-05-01 00:00:00

eissn

0306-5251

issn

1365-2125

pub_type

杂志文章

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The relationship between sunitinib exposure and both efficacy and toxicity in real-world patients with renal cell carcinoma and gastrointestinal stromal tumour.