Editor’s Note: This article was updated to remove an error referring to the objective response rate observed in the phase 3 AXIS trial.
In the past decade, a growing number of therapies have been approved for the treatment of metastatic renal cell carcinoma (RCC), including several that target the vascular endothelial growth factor (VEGF) pathway. Among those approved therapies is axitinib, a second-generation tyrosine kinase inhibitor (TKI) of VEGF receptors 1, 2, and 3.
“Prior to these drugs there really wasn’t effective treatment for these patients,” Brian I. Rini, MD, professor of medicine at the Cleveland Clinic in Ohio, told Cancer Therapy Advisor. “We used drugs called cytokines like interferon and interleukin 2, which did not work very well.”
A retrospective analysis of 6 clinical trials of interferon-alpha in advanced RCC showed a median overall survival (OS) of 13 months and a median time to progression of 4.7 months.1
In comparison, the phase 3 AXIS trial (ClinicalTrials.gov Identifier: NCT00678392) — which served as the basis for the US Food and Drug Administration (FDA)’s approval of the drug — showed that patients assigned to axitinib had a median progression-free survival (PFS) of 6.7 months.2 The study included 723 patients who were randomly assigned to axitinib 5 mg orally twice daily, or to sorafenib, a first-generation TKI, 400 mg twice daily. Treatment with axitinib significantly delayed progression compared with sorafenib (hazard ratio, 0.67; P < .0001).
The response rate was 19% for axitinib compared with 9% for sorafenib (P = .0001) and the median duration of response was 11 months.
“Probably about one-half to three-quarters of patients will have tumor shrinkage [with axitinib], a smaller amount of tumor shrinkage that doesn’t meet the criteria for response,” Dr Rini said. “One of the unusual features of the drug, from my experience, is that when people respond, it tends to be durable.”
In the AXIS trial, treatment with axitinib was associated with diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, hand-foot syndrome, decrease in weight, vomiting asthenia, and constipation.
“Axitinib can cause high blood pressure, which is relatively easily managed, and diarrhea and fatigue,” Dr Rini said.
A meta-analysis that included data from 10 trials evaluating axitinib showed an overall incidence of all-grade and high hypertension of 40.1% and 13.1%, respectively.3 Risk for all-grade hypertension with axitinib was significantly higher compared with other approved TKIs targeting VEGF receptors.