Intensified Monitoring of PhArmacology of Cabozantinib as a Tool for Toxicity Management in Patients With Renal Cell Carcinoma
Adverse events (AEs) with Cabozantinib are frequent (about 40-67% of patients) and often lead to temporary treatment interruptions, dose reductions or permanent discontinuations, potentially reducing dose intensity and sustained exposure. Therefore, strategies are needed to improve tolerability without compromising antitumor activity. Therapeutic drug monitoring (TDM) is particularly suitable for drugs with high interpatient variability, narrow therapeutic windows and defined exposure-response relationships; real world data support this profile for Cabozantinib and suggest that pharmacokinetically guided dosing could help manage toxicity while maintaining efficacy. Based on this evidence, the study proposes a model of individualized pharmacological counselling integrating TDM, pharmacogenetic testing and structured evaluation of pharmacological interactions to optimize Cabozantinib exposure and minimize avoidable toxicity.
• Patients diagnosed with histologically confirmed advanced/metastatic RCC with predominantly clear cell subtype.
• Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC, candidate to receive systemic treatment with nivolumab + Cabozantinib or Cabozantinib monotherapy as per clinical practice (investigators choice).
• Signed Written Informed Consent.
• Male or female subjects aged ≥18 years old.
• Women of childbearing potential must avoid pregnancy while on Cabozantinib. Female partners of male patients taking Cabozantinib must also avoid pregnancy. Effective methods of contraception should be used by male and female patients and their partners during therapy, and for at least 4 months after completing therapy. Because oral contraceptives might possibly not be considered as effective methods of contraception, due to factors such as missed doses, gastrointestinal disturbances, or potential drug interactions that could reduce their effectiveness, they should be used together with another method, such as a barrier method.
• Previous nephrectomy is permitted.
• All IMDC (International Metastatic RCC Database Consortium) risk (good, intermediate, poor).
• Eastern Cooperative Oncology Group performance status 0 or 1
• Capable of understanding and complying with the protocol requirements.
• patients will be included in the study regardless of their time of treatment start with Cabozantinib and regardless of their concomitant diseases or co-medication.
• Patients diagnosed with histologically confirmed advanced/metastatic RCC with predominantly clear cell subtype.
• Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC, candidate to receive systemic treatment with nivolumab + Cabozantinib or Cabozantinib monotherapy as per clinical practice (investigators choice).