Exposure-survival analyses of pazopanib in renal cell carcinoma and soft tissue sarcoma patients: opportunities for dose optimization

Autor: Jos H. Beijnen, Jan H.M. Schellens, Laurens E Swart, Alwin D. R. Huitema, Neeltje Steeghs, Remy B. Verheijen
Přispěvatelé: Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology
Rok vydání: 2017
Předmět:
Zdroj: Cancer Chemotherapy and Pharmacology, 80(6), 1171. Springer Verlag
Cancer Chemotherapy and Pharmacology
ISSN: 1432-0843
0344-5704
DOI: 10.1007/s00280-017-3463-x
Popis: BACKGROUND: Pazopanib is an angiogenesis inhibitor approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Post hoc analysis of a clinical trial demonstrated a relationship between pazopanib trough concentrations (Cmin) and treatment efficacy. The aim of this study was to explore the pharmacokinetics and exposure-survival relationships of pazopanib in a real-world patient cohort. PATIENTS AND METHODS: Renal cell cancer and soft tissue sarcoma patients who had at least one pazopanib plasma concentration available were included. Using calculated Cmin values and a threshold of > 20 mg/L, univariate and multivariate exposure-survival analyses were performed. RESULTS: Sixty-one patients were included, of which 16.4% were underexposed (mean Cmin 20 mg/L was related to longer progression free survival in renal cell cancer patients (34.1 vs. 12.5 weeks, n = 35, p = 0.027) and the overall population (25.0 vs. 8.8 weeks, n = 61, p = 0.012), but not in the sarcoma subgroup (18.7 vs. 8.8 weeks, n = 26, p = 0.142). In multivariate analysis Cmin > 20 mg/L was associated with hazard ratios of 0.25 (p = 0.021) in renal cancer, 0.12 (p = 0.011) in sarcoma and 0.38 (p = 0.017) in a pooled analysis. CONCLUSION: This study confirms that pazopanib Cmin > 20 mg/L relates to better progression free survival in renal cancer and points towards a similar trend in sarcoma patients. Cmin monitoring of pazopanib can help identify patients with low Cmin for whom individualized treatment at a higher dose may be appropriate.
Databáze: OpenAIRE
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