Bayer's announcement on sorafenib
11 January 2007
NEJM publishes evidence from largest ever placebo-controlled study in advanced kidney cancer to show median progression-free survival is doubled for patients treated with Nexavar (sorafenib)
Newbury, Berkshire, January 11, 2007 – Bayer HealthCare today announced the publication of encouraging Phase III data on sorafenib tablets - a treatment for patients with advanced renal cell carcinoma (RCC/kidney cancer), in the New England Journal of Medicine (NEJM).
Sorafenib is the first, multi-kinase inhibitor indicated for the treatment of patients with advanced RCC who have failed prior interferon-alpha or interleukin-2 based therapy and also 1st line when patients are considered unsuitable for such therapy.
Patients treated with sorafenib demonstrated a doubling of median progression-free survival (PFS) (5.5 months vs. 2.8 months) compared to patients receiving placebo (p-value< 0.001)1. The data, as assessed by independent radiologic review, are taken from the largest randomised controlled trial ever conducted in advanced RCC known as ‘Treatment Approaches in Renal Cancer Global Evaluation Trial’ – TARGET - study.
"Sorafenib and agents like it are exciting new treatments for patients with advanced kidney cancer who have no good standard options in this country at present, "said study investigator Tim Eisen, Professor of Medical Oncology, Cambridge. He added: "The vast majority of patients can tolerate treatment easily. The main job for us now is to secure these drugs for the NHS."
TARGET– a multi-national, randomised, placebo-controlled Phase III study of sorafenib administered as a single agent was initiated in 2003. More than 900 patients with advanced RCC, who had previously failed one prior systemic therapy, were enrolled in 117 sites worldwide and randomised into two treatment arms of equal numbers to receive either 400 mg sorafenib or placebo twice a day.
PFS measures the time that a patient lives without evident tumour growth. In a planned sub-group analysis the benefit in PFS was seen in all subgroups studied, including patients who had not received conventional treatment, such as interleukin-2 or interferon-alpha. After the PFS endpoint was met in April 2005, Bayer discussed the clinical and statistical significance of this analysis with the principal investigators, the independent data monitoring committee and with regulatory authorities and agreed that it would not be ethical to continue the study with a placebo-control arm. The study was subsequently modified and all patients in the trial were offered access to sorafenib.
A further interim analysis of overall survival (OS) based on 367 deaths and after 48% of the placebo patients (216 patients) had crossed over to sorafenib showed that median overall survival was 19.3 months for patients in the sorafenib group and 15.9 months for those in the placebo group (p=0.02). This analysis did not reach pre-specified O’Brien-Fleming boundaries for statistical significance.1In the phase III study, sorafenib was generally well tolerated. The most common reported treatment-emergent adverse events of any severity were diarrhoea, rash, fatigue, hand-foot skin reaction, alopecia, nausea, pruritus, hypertension, vomiting, erythema and dry skin.
