Study Reveals Survival Benefit for Patients With Inoperable Hepatocellular Carcinoma (HCC) Treated With a Unique Combination of Radioactive Microspheres and Standard-of-Care Systemic Therapy

CHICAGO, June 7, 2010 - A unique combination of liver targeted radioactive microspheres
(SIR-Spheres) and a standard-of-care systemic agent (Sorafenib) appears to
confer a survival benefit for patients with inoperable primary hepatocellular
cancer (HCC) including those with disease that has spread outside the liver,
according to the results of a prospective clinical study presented today at
the 46th American Society of Clinical Oncology (ASCO) conference. The
multi-center Phase II study was conducted by the Asia Pacific Hepatocellular
Carcinoma Trials Group (AHCC) headed by Professor Pierce Chow, Senior
Consultant, Singapore General Hospital and Visiting Senior Consultant,
National Cancer Center Singapore.

The Phase I/II trial was designed to evaluate tumor response and overall
survival in patients presenting with inoperable HCC in an
investigator-initiated prospective multi-center study which previously
reported the safety and tolerability of the combined therapies(1). Patients
with inoperable HCC with or without extra-hepatic spread and/or major
vascular involvement were eligible to receive treatment. Patients received
SIR-Spheres radioactive microspheres (Sirtex Medical Limited, Lane Cove,
Australia) targeted to the liver followed by sorafenib therapy
(Bayer-Schering Pharmaceuticals, Leverkusen, Germany) 11-14 days later. The
patients were followed monthly with clinic visits and an assessment of tumor
was conducted by CT scan every three months.

The results of the 35-patient study conducted in four countries in the
Asia-Pacific region (Singapore, South Korea, Myanmar and Malaysia) revealed a
median overall survival of 11.75 months. Overall survival for patients with
major vascular invasion (MVI) and/or extra-hepatic spread (EHS) vs. those
without MVI/EHS was 8.75 months and 18.25 months, respectively. This compared
very favorably with an overall survival of 5.6 months and 14.3 months
respectively in patients on sorafenib alone in a landmark Asia-Pacific
study(2). The overall tumor response rate was 35.5%, with 12% complete
response (CR), 23.5% partial response (PR), 44% stable disease (SD) and 21%
progressive disease (PD) with an overall disease control rate of 79.5%. Three
patients (9%) who initially presented with unresectable disease had a
sufficient reduction in tumor size to permit potentially curative therapy,
including 1 who had liver transplantation and 2 who received radio-frequency
ablation.

"The results of this study demonstrate that the combination of
radioactive microspheres and a systemic agent is a promising therapy for
patients with primary liver cancer, including those in whom the cancer has
spread outside the liver," said Professor Chow. "It is particularly
noteworthy that the response of tumors and median overall survival of 11.75
months in these difficult to treat patients are very favorable when compared
to the therapeutic effect of either agent alone. Patients in the advanced
stages of disease, particularly those with major vascular invasion in the
liver and spread of disease outside the liver are not candidates for
potentially curative therapies such as surgical resection, transplantation or
radio-frequency ablation(3). Thus these patients present with a very poor
prognosis with the expectation of limited survival. The combination of
SIR-Spheres and sorafenib confers a clear survival benefit in this patient
population who has limited treatment options available. Based on the results
of this study, we are very optimistic that the survival benefit observed for
this unique combination of the two agents will be confirmed by Phase III
studies."

Each year, approximately 1 million individuals are diagnosed with HCC
worldwide. Approximately 85% of these are not eligible for potentially
curative therapies such as resection, liver transplantation or
radio-frequency ablation due to the advanced stage of their disease(4).

About National Cancer Centre Singapore (NCCS)

The National Cancer Centre Singapore (NCCS) is the premier cancer
research and treatment facility in Singapore and in the region. It was
established in 1999 and sees about 68% of the public sector medical oncology
cases and about 65% of radiation oncology cases. NCCS not only houses the
most number of oncologists in Singapore but is also equipped with the largest
number of equipment to provide the latest radiation oncology care in
Singapore. For more information, visit NCCS website at www.nccs.com.sg.

Acknowledgement: This study was supported by grant NMRC/1161/2008 from
the National Medical Research Council Singapore and by Sirtex Medical and
Bayer-Schering Pharmaceuticals

References and Notes:

1. Chow PKH, Poon DYH, Choo SP et al. Phase I study of SIR-sphere plus
Sorafenib as first line treatment in patients with non-resectable
Hepatocellular Carcinoma. The Asia Pacific Hepatocellular Carcinoma Trials
Group protocol 05 (AHCC05). in 2009 American Society of Clinical Oncology
Annual Meeting 2009; Orlando.

2. Kang YK, Guan ZZ, Chen ZD et al. Sorafenib is effective in patients
from the Asia-Pacific with Hepatocellular Carcinoma: Subgroup analysis of
effect or macroscopic vascular invasion, extra-hepatic spread and ECOG
performance status on Outcome. in 59th Annual Meeting of the American
Association for the Study of Liver Diseases 2008. San Francisco.

3. Hung H. Treatment modalities for hepatocellular carcinoma. Current
Cancer Drug Targets 2005; 5 (2): 131-8.

4. El-Serag HB and Rudolph KL. Hepatocellular carcinoma: epidemiology and
molecular carcinogenesis. Gastroenterology 2007; 132 (7): 2557-76.

Andrea Moody, +1-919-244-4356, andrea.moody at fleishman.com, for Sirtex