Liver Cancer - Nexavar (sorafenib) Significantly Extends Overall Survival By 44% In Advanced Hepatocellular Carcinoma (HCC) Patients

Main Category: Liver Disease / Hepatitis
Also Included In: Cancer / Oncology
Article Date: 05 Jun 2007 - 1:00 PDT

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Data presented today at the 43rd annual meeting of the American Society of Clinical Oncology (ASCO) has shown that Nexavar (sorafenib) tablets significantly extended overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC), or primary liver cancer versus those taking placebo by 44% (HR=0.69; p-value=0.0006).1

The international, Phase III, placebo-controlled Sorafenib HCC Assessment Randomized Protocol (SHARP) Trial randomized and evaluated 602 liver cancer patients who had no prior systemic therapy at more than 100 sites worldwide including five in the UK*. The primary objective of the study was to compare OS in patients administered sorafenib versus those administered placebo. Median OS was 10.7 months in sorafenib-treated patients compared to 7.9 months in those taking placebo.1

"There are currently no licensed therapies in the UK or Europe that significantly improve survival for the thousands of patients with advanced HCC, which makes these results incredibly exciting. For the first time, we have a potential treatment option that has clearly been shown to significantly improve the overall survival of these patients. Sorafenib could provide a new standard of care for first-line treatment of advanced HCC", said Dr Dan Palmer, Senior Lecturer in Medical Oncology, University of Birmingham.

Bayer HealthCare halted the SHARP trial in February 2007 when an independent data monitoring committee determined that the overall survival endpoint had been met. There were no significant differences in serious adverse events between the sorafenib and placebo-treated groups.1 Based on the strength of the data, Bayer Healthcare is now in the process of preparing applications to the EMEA for a supplemental indication for sorafenib in treatment of patients with liver cancer. Sorafenib is currently licensed for renal cell carcinoma (RCC) / advanced kidney cancer when cytokines have failed or unsuitable.2

Penny Wilson-Webb from the Rarer Cancers Forum commented on these data saying: "Liver cancer is the fifth most common cancer worldwide with almost three thousand new cases in the UK each year. This treatment has the potential to make an enormous difference to those patients who currently have little or no options when diagnosed. Advances like this are long overdue."

Sorafenib is not licensed for use in HCC patients.

Renal Cell Carcinoma Overall Survival Data Presented At Asco:

Sorafenib is currently licensed for advanced Renal Cell Carcinoma (RCC, kidney cancer)2 when cytokines have failed or are unsuitable and has shown to increase median progression free survival (PFS) from 2.8 months to 5.5 months versus placebo (p<0.001) in the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) study, published in January this year in the New England Journal of Medicine.3 PFS measures the time that a patient lives without evident tumour growth.

Overall survival (OS) results for the kidney cancer TARGET study were presented yesterday at ASCO. The TARGET study was a multi-national, randomised, placebo-controlled Phase III study of sorafenib administered as a single agent. 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 to receive either 400 mg sorafenib or placebo twice a day. Median OS was 17.8 months in sorafenib-treated patients compared to 15.2 months in those taking placebo.4 (HR=0.88; p=0.146).** 4

TARGET study investigator Tim Eisen, Professor of Medical Oncology, Cambridge added; "The results of the interim analysis were sufficiently compelling - a doubling of Progression Free Survival (PFS) for the sorafenib patients - that all patients still in the placebo arm of the study were offered the opportunity to cross over onto sorafenib. This was done to allow all patients in the trial to benefit from the drug, despite the likelihood that the crossover of patients would confound the overall survival results of the trial. Nearly all of those who could cross over did so. Even those patients who started taking sorafenib late in the day appear to have benefited from treatment. The final overall survival data resulting from the TARGET study are consequently difficult to interpret."

Penny Wilson-Webb from the Rarer Cancers Forum stated; "We know that new treatment options in kidney cancer are making a real difference to people's lives. Extra time, free from the progression of their disease means more time left with family and friends and some people can even return to work - these things are invaluable for somebody with cancer."

* UK trial centres were based in Bristol, Glasgow, Newcastle and London (Royal Free Hospital & Guy's Hospital).

* * The final results were not found to be statistically significant however Bayer HealthCare is entirely satisfied that cross-over action taken in light of the strong PFS results for sorafenib at interim analysis confounded the OS results.

Glossary:

Progression Free Survival (PFS): The time that a patient lives without evident tumour growth

Overall Survival (OS): The time that a patient continues to live.

Renal Cell Carcinoma (RCC): The most common type of kidney cancer in adults

Hepatocellular Carcinoma (HCC): The most common form of primary liver cancer

Systemic Therapy: A drug which when administered affects the whole body and not just part of it.

About Sorafenib: When approved by the EMEA in July 2006, there had not been any new licensed 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 targets members of two classes of kinases (tyrosine kinases and serine/threonine kinases) known to be involved in tumour cell proliferation (tumour growth) and tumour angiogenesis (tumour blood supply) - two important cancer growth activities. These kinases include RAF kinase, VEGFR-2, VEGFR-3, PDGFR-β, 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 or are considered unsuitable for such therapy.

Bayer Healthcare is now in the process of preparing applications to the EMEA for a supplemental indication for Nexavar in treatment of patients with liver cancer.

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.

Nexavar 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. 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. www.bayerhealthcare.com

References

1. Llovet J. Sorafenib improves survival in advanced Hepatocellular Carcinoma (HCC): Results of a Phase III randomized placebo-controlled trial (SHARP trial). Presented at the American Society of Clinical Oncology (ASCO) annual meeting, 4th June, 2007
2. Nexavar Summary of Product Characteristics
3. Escudier B et al, New Engl J Med 2007 356 (2): 11-20
4. Bukowski R. Final results of the randomized phase III trial of sorafenib in advanced renal cell carcinoma: Survival and biomarker analysis. Presented at the American Society of Clinical Oncology (ASCO) annual meeting, 3rd June, 2007

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