| Abstract: |
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. © 2013 Elsevier Inc. All rights reserved. |
