Dr. Bernard Escudier provided an update on the sorafenib Phase III trial in patients with advanced renal cell carcinoma (RCC), or kidney cancer during the thirteenth European Cancer Conference (ECCO). Dr. Escudier is the head of immunotherapy and innovative therapy unit at the Gustave-Roussy Institute, Paris and co-principal investigator of the study along with Ronald Bukowski, director of the experimental therapeutics programme of The Cleveland Clinic Taussig Cancer Center, Cleveland, OH.
Dr. Escudier reported, based on an interim analysis, that there was an estimated 39 per cent improvement in survival for patients receiving sorafenib versus those receiving placebo. According to Dr. Escudier, "These data build on the previously announced finding that disease progression was significantly delayed in advanced kidney cancer patients who received sorafenib. As a clinician who regularly sees individuals suffering from this disease, I am encouraged by this growing body of data and what they may mean for patients and their families."
This interim analysis was conducted while the study was ongoing and soon after the Bayer Corporation and Onyx Pharmaceuticals decision to allow patients receiving placebo to cross over to treatment with sorafenib based on ethical considerations. The analysis was based on the 220 survival events (patient deaths) that had occurred by May 31, 2005. The final survival analysis, which is planned when 540 events have occurred, is not expected for some time. Therefore, while the findings of the interim analysis did not reach statistical significance, these early results suggest a favourable survival trend for patients who received sorafenib, states a Bayer release.
In June 2005, Dr. Escudier presented data from the same study, which demonstrated that sorafenib significantly prolonged progression-free survival. As independently reviewed, progression-free survival was doubled to a median value of 24 weeks in patients who received sorafenib as compared to 12 weeks for patients receiving placebo. In addition, 74 per cent of sorafenib patients had tumour shrinkage as compared to 20 per cent of placebo patients.
Based on the statistical and clinical significance of the progression-free survival data, Bayer and Onyx filed a new drug application (NDA) in July 2005 requesting approval in advanced renal cell cancer by the US FDA. Subsequently, the FDA granted the sorafenib filing priority review status, which means the agency will review the application with a goal of taking action within six months of receipt of the NDA. Additionally in September 2005, a marketing authorisation application (MAA) was submitted to the European Medicines Agency (EMEA) to market sorafenib in Europe.
In the Phase III trial, the rate of significant adverse events (grade 4) was comparable for patients receiving sorafenib or placebo. Grade 3 adverse events were modestly elevated in the sorafenib-treated group (31 per cent) as compared to placebo patients (22 per cent). Drug-related adverse events (all grades) were consistent with those observed in previous clinical trials and included: rash, diarrhoea, hand foot syndrome, hair loss, itching, nausea, hypertension, and fatigue.
Sorafenib (sorafenib tosylate) tablets, a novel investigational agent, are the first oral multi-kinase inhibitor that targets kinases in both the tumour cell and its vasculature. In preclinical models, Sorafenib blocked kinases known to be involved in proliferation (tumour growth) and angiogenesis (tumour blood supply) - two important cancer growth activities. These kinases included RAF kinase, VEGFR-2, VEGFR-3, PDGFR-ß, KIT, FLT-3, and RET.