Pharmacokinetics of Neoadjuvant Axitinib Influenced the Efficacy in Patients With Advanced Renal Cell Carcinoma.

Abstract

Although axitinib shows a good objective response rate and acceptable tolerability for advanced renal cell carcinoma, substantial differences in drug concentrations among individuals have hampered the reliable administration of the drug in a neoadjuvant setting. This study aimed to evaluate the relationship between axitinib pharmacokinetics and clinical efficacy in patients with advanced renal cell carcinoma treated in a neoadjuvant setting. We retrospectively reviewed 16 patients who underwent neoadjuvant axitinib treatment from prospective phase 2 study cohorts treated with axitinib and assessed whether the drug concentration was associated with clinical efficacy for primary tumors of advanced metastatic/oligometastatic clear cell renal cell carcinoma. Axitinib was administered orally at a starting dose of 5 mg twice daily for 2 months in principle before the operation, and the axitinib pharmacokinetics were examined. Best response, reduction rate, adverse events (AEs), and surgical complication were assessed. Four patients (25.0%) showed a partial response, and 12 (75.0%) had stable disease, with a mean reduction rate of 22.8%. No progressive disease was noted, and 9 of the 16 patinets (56.3%) showed downstaging. The trough level of axitinib significantly correlated with the objective response rate (P=.0052) and best tumor reduction (P=.0128). All AEs could be safely managed until termination of the dosing period. With respect to perioperative complications, grade 2 anemia was observed. Neoadjuvant axitinib treatment showed acceptable antitumor activity and safety profile for advanced renal cell carcinoma. The pharmacokinetics of neoadjuvant axitinib influenced the efficacy in patients with advanced renal cell carcinoma.