Although animal studies have suggested that sunitinib (Sutent) therapy may induce changes in tumor vessels or adaptations within tumors themselves that could promote cancer growth and metastasis, this does not occur in humans, according to new research.
Sunitinib, a tyrosine kinase inhibitor, was approved in January 2006 for the treatment of metastatic renal cell carcinoma (mRCC) on the basis of its ability to significantly delay time to tumor progression, and was subsequently shown to prolong survival, recounted Antonio Tito Fojo, MD, PhD, of the National Cancer Institute in Bethesda, Maryland, and colleagues in the Cell Press journal Cell Reports. A characteristic of RCC is high vascularity, and recent animal studies have raised the possibility that antiangiogenic agents might create a favorable environment for the acceleration of metastasis.
To address whether sunitinib accelerates tumors in humans, particularly after discontinuation, Fojo’s team analyzed data from the pivotal randomized phase III trial that led to the approval of the drug for mRCC. That trial compared sunitinib with interferon alfa in persons with mRCC.
After analyzing more than 10,000 data points from the trial, the researchers found no support for disease acceleration in persons receiving sunitinib, and demonstrated again that the drug is beneficial for patients with mRCC. “The evidence clearly shows that sunitinib was not harmful, did not accelerate tumor growth, and did not shorten survival,” Fojo and coauthors asserted in their report.
Specifically, neither longer treatment with sunitinib nor a greater effect of the drug on tumors reduced posttreatment survival. In fact, the longer patients stayed on sunitinib, the longer their overall survival. During sunitinib therapy the agent reduced tumor growth rate, thereby improving survival, without appearing to alter tumor biology after discontinuation.
These findings led Fojo’s group to conclude that concerns arising from animal models do not apply to humans receiving sunitinib and likely will not apply to similar agents. The investigators did point to several potential differences between the tumors in the mouse models and the tumors in humans that may account for the cancer-acceleration findings in mice but not in people.