SIR-Spheres(R) Y-90 Resin Microspheres Substantially Improves Quality of Survival in Primary Liver Cancer, New Study Against Standard Treatment Shows

PR68276

AMSTERDAM, Apr. 24, 2017 /PRNewswire=KYODO JBN/ --

         459-patient SARAH Study shows that local treatments of advanced or

inoperable   Hepatocellular Cancer (HCC) with SIR-Spheres Y-90 resin

microspheres did not lead to a   planned superiority difference in overall

survival compared to daily standard-of-care   systemic therapy with sorafenib,

yet had significantly reduced side effects and better Quality of Life

    Patients with advanced or inoperable Hepatocellular Carcinoma (HCC) who

usually received one or two treatments with liver-directed SIR-Spheres Y-90

resin microspheres in the 459-patient French SARAH study had similar survival

compared to patients who received standard twice-daily systemic treatment with

sorafenib, but with less than half the number and significantly fewer severe

treatment-related adverse effects and significantly better Quality of Life,

according to data presented here at The International Liver Congress(TM)

2017.[1]

(Logo: http://photos.prnewswire.com/prnh/20150119/724485 )

    The results, which could impact the treatment of tens of thousands of liver

cancer patients annually, were announced by the principal investigator of the

SARAH study, Professor Valerie Vilgrain MD, PhD, Department of Radiology,

Beaujon Hospital, Assistance Publique - Hopitaux de Paris (AP-HP) and

Universite Paris Diderot, Sorbonne Paris Cite, France.

    "Neither sorafenib nor SIR-Spheres Y-90 resin microspheres produced a

statistically significant difference in Overall Survival (OS) of the patients

we studied," said Prof. Vilgrain.  "Despite 26.6% of patients in the SIRT arm

not receiving SIR-Spheres per protocol, the primary endpoint of Overall

Survival by intention-to-treat [ITT] was not significantly different (median

8.0 vs. 9.9 months; p=0.18). Moreover, if we look at the patients who received

SIR-Spheres or sorafenib according to the SARAH protocol, median OS was

identical (9.9 vs. 9.9 months; p=0.92)."

    "In terms of what matters for patients, the findings from this first large

head-to-head comparison of liver-directed Selective Internal Radiation Therapy

(SIRT) and systemic chemotherapy with sorafenib also show clearly that

liver-directed procedures with SIR-Spheres result in a significantly better

tolerance of treatment and quality of life," Prof. Vilgrain stated.  "I believe

this consideration should be a critical factor in selecting first-line

treatment for this patient population in the future."

    The difference in the frequency and severity of side effects of patients

treated with SIR-Spheres Y-90 resin microspheres versus sorafenib was striking.

Significantly fewer patients treated with SIR-Spheres Y-90 resin microspheres

had any treatment-related side effects at all (76.5% vs. 94.0% for sorafenib;

p＜0.001), and these were also less severe (greater than or equal to grade 3;

40.7% vs. 63.0%, respectively; p＜0.001). Moreover, those patients treated with

SIR-Spheres Y-90 resin microspheres who reported treatment-related side effects

experienced a median of only 5 such events over the course of the SARAH study,

compared to a median of 10 events in those who received sorafenib (p＜0.001).

    General treatment-related symptoms such as fatigue (42% vs. 65%; p＜0.001),

abdominal pain (20% vs. 29%; p=0.032), nausea or vomiting (12% vs. 23%;

p=0.001) and infection (4% vs. 11%; p=0.007) were also significantly less

frequently reported and less severe for patients receiving SIR-Spheres Y-90

resin microspheres, compared to sorafenib.

    Fewer patients receiving SIR-Spheres Y-90 resin microspheres experienced

treatment-related diarrhoea (13% vs. 68% for sorafenib; p＜0.001), hand-foot

skin reaction (0.4% vs. 21%; p＜0.001), anorexia (13% vs. 32%; p＜0.001), weight

loss (6% vs. 21%; p＜0.001)  and alopecia (0% vs. 16%; p＜0.001), as well as

infections (4% vs. 11%; p=0.007), hypertension (3% vs. 13%; p＜0.001) and

non-gastrointestinal haemorrhage (3% vs. 10%; p=0.002).

    There were few potential SIRT-associated treatment-related complications

and, importantly, no radioembolization-induced liver disease (radiation

hepatitis) experienced. There were no significant increases for SIR-Spheres

Y-90 resin microspheres in gastrointestinal (GI) ulceration (2% vs. 0.5% for

sorafenib; p=0.37) including one case of radiation-induced GI ulcer, ascites

(12% vs. 11%; p=0.57), hyperbilirubinemia (12% vs. 13%; p=0.86) and only one

case of radiation pneumonitis (0.4% vs. 0; p=0.46).

    The results of Quality of Life (QoL) surveys filled out by SARAH

participants at three month intervals after their initial treatment underscored

the benefit of SIR-Spheres Y-90 resin microspheres. "Based on their responses

to the Global Health Status questions in the European Organisation for Research

and Treatment of Cancer [EORTC] QLQ-C30 questionnaire, patients treated with

SIR-Spheres maintained their health status over the duration of the SARAH

study, whereas patients receiving sorafenib reported a significant and

sustained decline in QoL (group effect: p=0.005; time effect: p＜0.001; between

group difference increase over time: p=0.045)," Prof. Vilgrain said.

    "In addition," she noted, "we found that the tumours of patients treated

with SIR-Spheres had a higher objective response (19.0% vs. 11.6%; p=0.042)

than was seen with sorafenib, and experienced a significantly reduced risk of

their cancer progressing in the liver, which is the main cause of death from

this disease."

                               Background of the SARAH Study

    "Patients with HCC who are not eligible for liver transplant, surgery or

ablation to treat their tumours in place face a very bleak prognosis of one or

two years of life with increasing debilitation and pain," Prof. Vilgrain said.  

"In many cases, the patient's HCC is already so advanced that the main

treatment option available is sorafenib. In other cases, we are able to treat

patients with intermediate-stage disease initially with several courses of

chemotherapy infused directly into their livers, which is called transarterial

chemoembolisation, or TACE, but this approach may fail."

    "For patients with advanced HCC or those failing TACE, we have for the past

ten years relied upon oral systemic treatment with sorafenib, which was shown

to extend survival compared to placebo, but also causes many side effects that

can compromise patients' quality of life.  That is why we decided to see if

treatment with a newer form of liver-directed therapy, selective internal

radiotherapy, or SIRT, with SIR-Spheres could represent a better alternative.  

Our decision to initiate the SARAH study was based on smaller previous studies

and retrospective analyses, which suggested that SIR-Spheres could be at least

as effective and was well tolerated by HCC patients," she stated.

    The randomized, controlled, open-labelled SARAH (SorAfenib versus

Radioembolization in Advanced Hepatocellular carcinoma) study directly compared

the efficacy of selective internal radiation therapy (SIRT, or

radioembolisation) using yttrium-90 [Y-90] resin microspheres (SIR-Spheres Y-90

resin microspheres, Sirtex Medical Limited, Sydney, Australia) versus sorafenib

(Nexavar(R), Bayer HealthCare Pharmaceuticals, Berlin, Germany).

    SARAH was launched in December 2011 and concluded enrolment in February

2015.

    With 459 patients treated in 25 clinical centres across France, SARAH is

the largest randomized study ever to compare selective internal radiation

therapy - or any liver-directed therapy - against the standard-of-care systemic

therapy in the treatment of primary liver cancer.  Almost 70% of the patients

in the SARAH study had advanced HCC (Barcelona Clinic Liver Cancer stage C),

with portal vein thrombosis and no extrahepatic spread. Most of the other

patients had failed two cycles of TACE.

    Results of SIRveNIB, a parallel study in more than 360 Asia Pacific HCC

patients will be presented at the American Society of Clinical Oncology (ASCO)

Annual Meeting in Chicago on 4 June 2017.

                          What is Hepatocellular Carcinoma (HCC)?

    HCC patients represent 90% of all people diagnosed with primary liver

cancer, which is the sixth most common cancer in the world and the second

leading cause of cancer-related death.  HCC affects mainly patients with

cirrhosis from any cause, including viral hepatitis, alcohol misuse, and fatty

liver disease, and results in more than 670,000 deaths globally each year.[2]

Among people at risk of HCC, incidence of the disease increases progressively

with advancing age, reaching a peak at around 70 years.[3]

    Overall, one-third of patients with liver cirrhosis will develop HCC during

their lifetime.[4]

- Worldwide, approximately 54% of HCC cases can be attributed to HBV infection

(affecting 400 million people) while 31% can be attributed to HCV infection

(affecting 170 million people).[3]     

- In Africa and East Asia, the largest attributable fraction is due to HBV

infection (60%), while in the developed Western world, chronic HCV infection

appears to be the major risk factor.[5],[6]

    In addition to these causes, it is now thought that up to one in eight

(12.8%) of non-alcoholic steatohepatitis (NASH) patients with cirrhosis will

progress to HCC.[7] NASH - which is widely considered to be triggered by type

II diabetes, insulin resistance, obesity, hyperlipidaemia and hypertension -

has become the number one cause of liver disease in Western countries.  

Progression of NASH dramatically increases the risks of cirrhosis, liver

failure, and HCC.  This is thought to be related to the worldwide epidemic of

diabetes and obesity.[8]

    HCC occurs more often in men than women, except in Africa, where more women

are affected.[2]

                   What is SIRT with SIR-Spheres Y-90 resin microspheres?

    SIRT with SIR-Spheres Y-90 resin microspheres is an approved treatment for

inoperable liver tumours. It is a minimally-invasive treatment that delivers

high doses of high-energy beta radiation directly to the tumours.  SIRT is

administered to patients by interventional radiologists, who infuse millions of

radioactive resin microspheres (diameter between 20-60 microns) via a catheter

into the liver arteries that supply blood to the tumours. By using the tumours'

blood supply, the microspheres selectively target liver tumours with a dose of

radiation that is up to 40 times higher than conventional radiotherapy, while

sparing healthy tissue.

    SIR-Spheres Y-90 resin microspheres are approved for use in Argentina,

Australia, Brazil, the European Union (CE Mark), Switzerland, Turkey, and

several countries in Asia for the treatment of unresectable liver tumours. In

the US, SIR-Spheres Y-90 resin microspheres have a Pre-Market Approval (PMA)

from the FDA and are indicated for the treatment of unresectable metastatic

liver tumours from primary colorectal cancer with adjuvant intra-hepatic artery

chemotherapy (IHAC) of FUDR (floxuridine).

    References:

1) Vilgrain V et al.  The International Liver Congress(TM) 2017 - 52nd annual

meeting  of the European Association for the Study of the Liver, J Hepatol

2017; 66 (Suppl 1):       Abs. GS-012.     

2) Extrapolated from Ferlay J et al.  Globocan 2012. v1.0, Cancer Incidence and

Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France:

International Agency for Research on Cancer; 2013. Available from:

http://globocan.iarc.fr, accessed on 14/April/2017.     

3) EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular

carcinoma. J       Hepatol 2012; 56: 908-43.     

4) Sangiovanni A et al.  Hepatology 2006; 43: 1303-10.     

5) Di Bisceglie AM.  Hepatology 2009; 49(Suppl 5): S56-60.     

6) Davis GL et al.  Proc (Bayl Univ Med Cent) 2008; 21: 266-80     

7) White DL et al.  Clin Gastroenterol Hepatol 2012; 10: 1342-59.     

8) World Gastroenterology Organisation Global Guidelines: Nonalcoholic Fatty

Liver       Disease and Nonalcoholic Steatohepatitis, 2012.

    SIR-Spheres(R) is a Registered Trademark of Sirtex SIR-Spheres Pty Ltd.

    562-EUA-0417

SOURCE: Sirtex Medical Limited