Five-Year Survival in Patients With Cytokine-Refractory Metastatic Renal Cell Carcinoma Treated With Axitinib

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• 作者：Brian I. Rini¹ ; ^{rinib2@ccf.org} ; Thibault de La Motte Rouge² ; Andrea L. Harzstark³ ; M. Dror Michaelson⁴ ; Glenn Liu⁵ ; Viktor Grü ; nwald⁶ ; Antonella Ingrosso⁷ ; Michael A. Tortorici⁸ ; Paul Bycott⁸ ; Sinil Kim⁸ ; Joanna Bloom⁹ ; Robert J. Motzer¹⁰
• 关键词：Long-term survival ; Pharmacokinetics ; Tyrosine kinase inhibitor ; Vascular endothelial growth factor receptor inhibitor
• 刊名：Clinical Genitourinary Cancer
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：11
• 期：2
• 页码：107-114
• 全文大小：442 K

文摘

Background

In a phase II study of axitinib for cytokine-refractory metastatic renal cell carcinoma, median overall survival (OS) was 29.9 months (95 % CI, 20.3 to not estimable months).

Patients and Methods

Long-term survival data were collected retrospectively from 52 patients with cytokine-refractory metastatic renal cell carcinoma who received axitinib in a completed phase II study (protocol 1), 11 of whom enrolled in a continuing access protocol (protocol 2), for the current observational study (protocol 3). In a post hoc analysis, the patients were grouped into quartiles based on cycle 1 day 1, 1- to 2-hour post-dose axitinib plasma levels to explore the impact of drug exposure on efficacy.

Results

The 5-year survival rate was 20.6 % (95 % CI, 10.9 % -32.4 % ), with a median follow-up of 5.9 years. Frequent all-grade adverse events were fatigue (n = 38; 73.1 % ), diarrhea (n = 34; 65.4 % ), hypertension (n = 33; 63.5 % ), and nausea (n = 33; 63.5 % ). Quartile 3 patients (axitinib level, 45.2-56.4 ng/mL; n = 12) had the best clinical outcome: objective response rate 82 % , median progression-free survival (PFS) 28.3 months, and median OS that was not reached after 5 years.

Conclusions

Axitinib was well tolerated and provided an estimated 5-year survival rate of 20.6 % for cytokine-refractory metastatic renal cell carcinoma. Exploratory analyses showed numerically higher objective response rate and longer OS and PFS in patients who achieved post-first-dose axitinib plasma concentrations within a specific range.