78P - The integration of TDM and PGx in patients with mRCC receiving sunitinib treatment

Background

Sunitinib (SUN), used to treat metastatic renal cell carcinoma (mRCC), shows significant variability in drug exposure and therapeutic response among patients (pts). Flat dosing may lead to either under- or over-exposure in different pts. Therapeutic Drug Monitoring (TDM) and pharmacogenetic (PGx) assessment could assist in optimizing treatment outcomes. This study aimed to evaluate the feasibility and clinical utility of intensified pharmacological counseling through TDM and PGx for SUN treatment in mRCC.

Methods

Blood samples were collected at minimum steady-state plasma concentration (C_min) from pts enrolled in the CRO-2022-14 trial. Plasma exposure was evaluated by measuring SUN level using a validated LC-MS/MS method. Target C_min ranges for effective and safe treatment were defined as 37.5 to 60-75 ng/mL for continuous dosing and 50 to 80-87.5 ng/mL for intermittent dosing. Genetic polymorphisms related to SUN metabolism and transport were assessed. Oncologists received an integrated pharmacological report based on the analyzed data.

Results

Eight pts on SUN therapy, with a median treatment duration of 34 months at baseline, were enrolled. Six pts were receiving reduced dose based on clinical toxicity. Six pts achieved mean C_min between 53 and 68 ng/mL, aligning with the target exposure for effective and safe therapy. One patient showed a mean C_min of 84 ng/mL despite a reduction to 25 mg/day, with recurrent Grade 2 (G2) toxicity, suggesting the need for a potentially lower, effective dose. Another patient, who received 25 mg/day due to G3 toxicity, reached a C_min of 39 ng/mL, with no further severe toxicities observed; thus, a higher dose (37.5 mg/day) might have been considered to maintain the exposure within range. PGx analyses were performed, though the small sample size limited conclusive findings.

Conclusions

Toxicity-driven dose adjustment led to adequate SUN exposure for most patients in a 34-months average treatment duration. Early implementation of TDM could have optimized dosing in earlier treatment phases, potentially enhancing tolerance and adherence while ensuring adequate plasma exposures. Intensified pharmacological counseling was shown to be both feasible and clinically useful.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Fratino L., MD.

Funding

Has not received any funding.

Disclosure

F. Puglisi: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Daiichi Sankyo, Viatris, Celgene, Eisai , Eli Lilly, Exact Sciences, Gilead, Ipsen, Italfarmaco, Menarini, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen , Takeda; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Daiichi Sankyo, Viatris, Celgene, Eisai, Eli Lilly, Exact Sciences, Gilead, Ipsen, Italfarmaco, Menarini, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Takeda; Financial Interests, Personal, Research Grant: Amgen, AstraZeneca, Daiichi Sankyo, Viatris, Celgene, Eisai, Eli Lilly, Exact Sciences, Gilead, Ipsen, Italfarmaco, Menarini, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Takeda; Financial Interests, Personal, Other, travel grants: amgen, AstraZeneca, Daiichi Sankyo, Viatris, Celgene, Eisai, Eli Lilly, Exact Sciences, Gilead, Ipsen, Italfarmaco, Menarini, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Takeda. All other authors have declared no conflicts of interest.