Therapeutic Monitoring of Sunitinib Shows Potential in Adults With GIST and Metastatic RCC

Review findings support the use of sunitinib dose modification guided by therapeutic drug monitoring in certain patients with renal cell carcinoma (RCC) and gastrointestinal stromal tumors (GIST; Ther Drug Monit. 2020;42[1]:20-32).

Sunitinib therapy is standard-of-care for patients with advanced and metastatic RCC and a second-line treatment option for patients with locally advanced, inoperable, and metastatic GIST, according to Regina Demlová, PhD, Department of Pharmacology, Medical Faculty, Masaryk University, Brno, and colleagues.

“A fixed dose of the drug, however, does not produce a uniform therapeutic outcome in all patients, and many face adverse effects and/or toxicity. One of the possible causes of the interindividual variability in the efficacy and toxicity response is the highly variable systemic exposure to sunitinib and its active metabolite,” they said.

With this in mind, Dr Demlová et al conducted a review with the purpose of summarizing all available clinical evidence for the treatment of adults with sunitinib in approved indications. They also sought to address the need for robust and appropriate therapeutic drug monitoring of sunitinib and its major metabolite, N-desethylsunitinib.

Using PubMed, the investigators performed a systematic search of available scientific literature using relevant search terms. Of 520 journal articles identified, 447 were excluded because of a lack of sufficient relevance to the reviewed topic, leaving 73 articles open to thorough review alongside currently valid guidelines.

Based on their review, Dr Demlová stated that there is sufficient evidence confirming the concentration-efficacy and concentration-toxicity relationship in the indications of sunitinib for patients with GIST and metastatic RCC.

Of note, they posited that total (sunitinib plus N-desethylsunitinib) trough levels of 50 ng/mL to 100 ng/mL serve as a reasonable target therapeutic range for optimal therapeutic response, and that total trough levels should not be >100 ng/mL to avoid toxicity.

“According to the current evidence presented in this review, a TDM [therapeutic drug monitoring]-guided dose modification of sunitinib in selected groups of patients could provide a better treatment outcome while simultaneously preventing sunitinib toxicity,” concluded Dr Demlová and colleagues.—Hina Porcelli