Relationships of serum cabozantinib concentration with tumor response and adverse events in treatment of advanced renal cell carcinoma: observational exploratory prospective study.

backgroundSevere adverse events frequently occur in patients treated with cabozantinib in routine clinical care, and suboptimal responses to cabozantinib are seen in certain patients. In this prospective and observational clinical study, we investigated cabozantinib concentration-response and concentration-toxicity relationships. PATIENTS AND

methodsWe examined twelve patients with renal cell carcinoma treated with cabozantinib monotherapy between March 2021 and March 2024. We assessed the association of serum trough cabozantinib concentrations with the best tumor shrinkage rates. We also evaluated the association between trough cabozantinib concentrations and occurrence of adverse events.

resultsThere was a significant positive correlation between the concentrations of cabozantinib and the best tumor shrinkage rates (R = 0.64, p = 0.026). The trough cabozantinib concentration was significantly lower in patients without adverse events than patients with grade ≥ 1 adverse events, such as increased aspartate aminotransferase (p = 0.003), hand-foot syndrome (HFS) (p = 0.025), increased alanine aminotransferase (p = 0.008), hoarseness (p = 0.026), and dysgeusia (p < 0.001). Furthermore, there were significant differences in the trough cabozantinib concentrations between patients with grade ≤ 1 and patients with grade ≥ 2 adverse events, including hypertension (p = 0.019) and HFS (p = 0.038).

conclusionIn patients with renal cell carcinoma, serum cabozantinib concentrations were correlated with maximum tumor shrinkage rates in a clinical setting. This study also suggested that the occurrence of adverse events, such as HFS and hypertension, is associated with the serum concentrations of cabozantinib.