Sorafenib demonstrated efficacy in an ongoing Phase III trial in patients with advanced renal cell carcinoma ( RCC ), or kidney cancer.

Sorafenib, a novel investigational drug candidate, is the first oral multi-kinase inhibitor that targets serine/threonine and receptor tyrosine kinases in both the tumor cell and tumor vasculature.
In preclinical models, Sorafenib targeted members of two classes of kinases known to be involved in both tumor cell proliferation and tumor angiogenesis - two important cancer growth activities.
These kinases included RAF kinase, VEGFR-2, VEGFR-3, PDGFR-ß, KIT, FLT-3 and RET.

More than 900 patients with advanced kidney cancer, who had previously failed one prior systemic therapy, have been enrolled in the study.
Participating patients were randomized one-to-one to receive either 400 mg Sorafenib or placebo twice a day.

The primary endpoint of the study is overall survival, with progression-free survival ( PFS ), overall response rate, quality of life, and safety also being assessed.

Tumors were evaluated using RECIST criteria.

Bernard Escudier, of the Gustave-Roussy Institute, Paris, reported that disease progression was significantly delayed in those patients who received Sorafenib.

As assessed by independent radiologic review, a measure of disease progression called PFS was doubled to a median value of 24 weeks ( 167 days ) in patients receiving Sorafenib as compared to 12 weeks ( 84 days ) for patients receiving placebo ( p < 0.000001 ).

" We now have randomized data documenting that Sorafenib substantially delays tumor growth in patients with advanced RCC, " said Escudier. " At the same time, the side effects observed were readily managed in the clinical setting. This randomized data is important since advanced renal cancer is a disease with differences among patient populations that can make comparisons to historical controls unreliable. These results underscore the clinical significance of disease control as an important measure of therapeutic benefit. "

Bernard Escudier is co-principle investigator of the Phase III study along with Ronald Bukowski, of The Cleveland Clinic - Taussig Cancer Center, Cleveland.

There were 768 patients evaluated for safety.
Drug-related adverse events ( all grades ) were similar to what has been observed in previous clinical trials and included rash, diarrhea, hand foot syndrome, hair loss, itching and nausea, hypertension, and fatigue.

Source: 41st Annual Meeting of the American Society of Clinical Oncology ( ASCO ), 2005


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