Everolimus improves survival with advanced renal cancer

July 23, 2008

NEW YORK (Reuters Health) - Treatment with everolimus, a mammalian target of rapamycin (mTOR) inhibitor, can significantly improve progression-free survival in patients with advanced renal cell carcinoma that has not responded to other targeted therapies, according to a report in the July 23rd online issue of The Lancet.

This finding stems from a study of 410 patients with metastatic renal cancer that had progressed on sunitinib, sorafenib, or both drugs. The subjects were randomized to receive everolimus 10 mg once daily or placebo in addition to best supportive care.

The study was initially set to stop after 290 progression events had been logged, but an interim analysis showed a clear advantage with everolimus therapy so the trial was terminated after 191 events, lead author Dr. Robert J. Motzer, from Sloan-Kettering Cancer Center in New York, and colleagues note.
Overall, the prevalence of progression events in the everolimus group was 37% compared with 65% in the control group (p < 0.0001). The corresponding median progression-free survival periods were 4.0 and 1.9 months.

Stomatitis, rash, and fatigue were more common in the everolimus group than in the placebo group but were usually of mild or moderate severity, the researchers note. Twenty-two patients (8%) in the everolimus group developed pneumonitis, which was of grade 3 severity in 8 patients.

In a related editorial, Dr. Jennifer J. Knox, from the University of Toronto, comments that "routine use of progression-free survival as a surrogate for clinical benefit is not acceptable."
She adds, however, that "data for treatment of metastatic renal cell carcinoma...support (the) choice of this design," and concludes: "I would encourage international regulatory boards to accept these data as evidence of clinical benefit."

Copyright Thomson Reuters 2008. Click for Restrictions