Advanced Kidney Cancer - Median Progression-free Survival Doubled For Patients Treated With Nexavar (sorafenib), Phase III Data

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.В  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. 1

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) В 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.1

In 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.2

About Sorafenib:

When launched in July 2006, sorafenib was the first new kidney cancer treatment in Europe for over 10 years.

Mechanism of Action:

Sorafenib is an oral multi-kinase inhibitor that targets both the tumour cell and tumour vasculature. In preclinical models, sorafenib targeted members of two classes of kinases (tyrosine kinases and serine/threonine kinases) known to be involved in both tumour cell proliferation (tumour growth) and tumour angiogenesis (tumour blood supply) - two important cancer growth activities. These kinases included RAF kinase, VEGFR-2, VEGFR-3, PDGFR-ОІ, c-KIT and FLT-3.2

Indication:

Sorafenib, (200 mg film-coated tablets) is indicated for the treatment of patients with advanced renal cell carcinoma who have failed prior interferon-alpha or interleukin-2 based therapy and also 1st line when patients are considered unsuitable for such therapy.2

Sorafenib is being evaluated as a single agent in a Phase III clinical trial for the treatment of advanced hepatocellular carcinoma (HCC), or liver cancer, a study that has completed enrolment. A Phase III clinical trial of Nexavar combined with carboplatin and paclitaxel in non-small cell lung cancer (NSCLC) for treatment-naive patients was initiated in the first half of 2006. In addition to company-sponsored trials, there are a number of sorafenib studies being sponsored by government agencies, cooperative groups, and individual investigators.

About Kidney Cancer:

The Disease:

More than 6,600 people are diagnosed with kidney cancer each year in the UK. Kidney cancer causes around 3,600 deaths each year in the UK.3 In adults in England and Wales almost 90% of malignant kidney tumours arise in the renal parenchyma and the renal pelvis.3 Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, causing up to 85 percent of all kidney cancers.4

Key Statistics:

Kidney cancer affects both men and women with a ratio of 5 new diagnoses in men for every 3 in women3 Between 1975 and 2002, the incidence of kidney cancer in the UK has almost doubled for both men and women aged over 65 years.3

In men incidence rates increased by 79% between 1975 and 2002 (from 7.1 in 100,000 in 1975 to 12.7 per 100,000 in 2002), and by 90% in women (from 3.2 to 6.1 per 100, 000) over the same time period, mainly affecting men over 65 and women over 55 years.3

Risk Factors:

The major risk factors for kidney cancer include age and sex, obesity, smoking, and several genetic and medical conditions. Other factors such as phenacetin use and occupation also increase risk but these exposures are not widespread and most likely account for a small number of cases.5

Symptoms:

In the early stages kidney cancer does not generally cause any symptoms.3

Late symptoms include6: blood in the urine - haematuria; low back pain unrelated to injury; a lump in the abdomen in the region of the kidneys; fatigue; weight loss; recurrent fevers not associated with colds or flu; high blood pressure; swelling of the ankles and legs.

Treatment:

The treatment of kidney cancer depends on the severity of the cancer and the patient's overall health. The main treatment for kidney cancer is surgery4, which is effective when all of the cancer is removed.

For further information please visit: http://info.cancerresearchuk.org

Nexavar(R) is a registered trademark of Bayer Pharmaceuticals Corporation.

About Bayer HealthCare:

Bayer HealthCare AG, with sales of approximately 9.4 billion Euros in 2005, is one of the world's leading, innovative companies in the healthcare and medical products industry. The company combines the global activities of the Animal Health, Consumer Care, Diabetes Care and Pharmaceuticals divisions. Bayer Pharmaceuticals Corporation is part of the new Global Pharmaceutical Division, established January 1, 2006, which consists of the former Biological Products and Pharmaceutical Division and now comprises three business units: Haematology/Cardiology; Oncology and Primary Care.В  Bayer HealthCare AG employed 33,800 people worldwide in 2005.

Bayer HealthCare AG's aim is to discover and manufacture innovative products that will improve human and animal health worldwide. The products enhance well-being and quality of life by diagnosing, preventing and treating disease.

http://www.bayerhealthcare.com

References:

1. Escudier B et al, New Engl J Med 2007 356 (2): 11-20
2. В Nexavar Summary of Product Characteristics
3. Cancer Research UK, Cancer Statistics by Type, kidney cancer
4. Cohen N. N Engl J Med, 2005; 353:В  2477-2490
5. Quin, M., et al. Cancer Trends in England and Wales 1950-1999. ed., Vol. SMPS No. 66. 2001: TSO
6. American Cancer Society, Detailed Guide: Kidney Cancer - Surgery