Data from Pazopanib Exposure Relationship with Clinical Efficacy and Safety in the Adjuvant Treatment of Advanced Renal Cell Carcinoma

• DOI: 10.1158/1078-0432.c.6525795.v1
• Publication Date: 2023-04-01T06:30:48Z
• Authors: Cora N. Sternberg; Frede Donskov; Naomi B. Haas; Christian Doehn; Paul Russo; Mohamed Elmeliegy; Guillaume Baneyx; Hiya Banerjee; Paola Aimone; Robert J. Motzer
• Keywords: Pazopanib; Quartile

<div>Abstract<p><b>Purpose:</b> PROTECT, a phase III, randomized, placebo-controlled study, evaluated pazopanib efficacy and safety in the adjuvant renal cell carcinoma setting. The relationship between exposure (C<sub>trough</sub>) was evaluated.</p><p><b>Patients Methods:</b> Evaluable steady-state blood trough concentrations were collected from 311 patients at week 3 or 5 (early C<sub>trough</sub>) 250 16 20 (late C<sub>trough</sub>). Pazopanib pharmacokinetic (PK) data analyzed via population model approach. Relationship C<sub>trough</sub> dose intensity disease-free survival (DFS) explored Kaplan–Meier multivariate analysis. Adverse events (AE) AE-related treatment discontinuation proportions summarized by quartiles.</p><p><b>Results:</b> Most (>90%) with early late started on 600 mg. Mean overlapped across levels. Patients higher quartiles achieved longer DFS (adjusted HR, 0.58; 95% confidence interval, 0.42–0.82; <i>P</i> = 0.002). achieving >20.5 μg/mL had significantly DFS: not estimable (NE) versus 29.5 months, 0.006, NE 29.9 0.008, respectively. Dose up to 8 did correlate DFS, consistent PK model–based simulations showing overlapping 800 mg doses. proportion of grade 3/4 AEs, exception hypertension, correlated C<sub>trough</sub>.</p><p><b>Conclusions:</b> In setting, associated improved increase discontinuations hypertension. <i>Clin Cancer Res; 24(13); 3005–13. ©2018 AACR</i>.</p><p><i>See related commentary Rini, p. 2979</i></p></div>