Long-Term Safety With Axitinib in Previously Treated Patients With Metastatic Renal Cell Carcinoma.

Abstract

BACKGROUND:

Axitinib is an approved treatment for advanced renal cell carcinoma (RCC) after failure of 1 systemic therapy.

PATIENTS AND METHODS:

Long-term safety with single-agent axitinib was analyzed using pooled data from clinical trials in 672 previously treated patients with metastatic RCC (mRCC) and in 1304 patients with different advanced solid tumors. In all studies, except the phase I first-in-human, dose-finding study, the starting dose of oral axitinib was 5 mg twice daily continuously. Common long-term treatment-emergent adverse events (AEs) were identified in patients who received axitinib for ≥ 2 years, then evaluated in all patients, and assessed using interval, cumulative, and latency analyses.

RESULTS:

In all, 108 (16%) previously treated patients with mRCC received axitinib for ≥ 2 years. In interval analysis, most AEs occurred during the first 6 months of treatment, with rates stable or decreased over time; rates increased for proteinuria, peripheral edema, and increased blood creatinine. Common Grade ≥ 3 AE rates declined or plateaued over time, except for increased amylase and myocardial infarction. Results were similar in cumulative analysis in this population, and in interval and cumulative analyses in all patients with mRCC and those with advanced solid tumors.

CONCLUSION:

Declining or stable rates of most AEs support an acceptable long-term safety profile for axitinib in patients with mRCC. However, increases in the rates of some AEs warrant monitoring. This analysis is limited in that it was retrospective and included a relatively small patient population.

• Authors: Brian I Rini, Bernard Escudier, Subramanian Hariharan, W Gregory Roberts, Jamal Tarazi, Brad Rosbrook, Zena Askerova, Liza L DeAnnuntis, Robert J Motzer
• Journal: Clinical genitourinary cancer (Clin Genitourin Cancer) Vol. 13 Issue 6 Pg. 540-7.e1-7 (Dec 2015) ISSN: 1938-0682 [Electronic] United States
• PMID: 26320662 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Imidazoles
• Indazoles
• Protein Kinase Inhibitors
• Axitinib

Topics

• Axitinib
• Carcinoma, Renal Cell (drug therapy)
• Drug Administration Schedule
• Female
• Humans
• Imidazoles (administration & dosage, adverse effects)
• Indazoles (administration & dosage, adverse effects)
• Kidney Neoplasms (drug therapy)
• Male
• Neoplasm Metastasis
• Protein Kinase Inhibitors (administration & dosage, adverse effects)
• Retrospective Studies