PR66091

New European Society of Medical Oncology (ESMO) Biliary Cancer Guidelines Indicate Selective Internal Radiation Therapy (SIRT) with Y-90 Microspheres as an Option for Post-Chemotherapy Treatment of Intrahepatic Cholangiocarcinoma (iCCA)

SYDNEY, Oct. 11, 2016 /PRNewswire=KYODO JBN/ --

      Sirtex Medical Limited (ASX: SRX) announced today that the European

Society of Medical Oncology (ESMO) has indicated the use of SIRT using

yttrium-90 (Y-90) microspheres as an option in for the treatment of

intrahepatic cholangiocarcinoma (iCCA), a form of primary liver cancer that

starts in the bile duct, the branching network of thin tubes that deliver

fat-digesting bile from the liver to the small intestine.[1]

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

    The new ESMO guidelines on biliary cancers were published in September 2016

as a supplement to the Annals of Oncology.[1] Their lead author, Professor Juan

Valle, department of medical oncology, Christie NHS Foundation Trust,

University of Manchester, UK, states that selective internal radiation therapy

(SIRT), which is also known as radioembolisation, "may be considered in

patients with inoperable iCCA, usually after first-line chemotherapy."

    The ESMO inclusion of SIRT for the treatment of iCCA was based on ESMO's

review of a pooled analysis of 12 studies totalling 298 patients that was

published in the European Journal of Surgical Oncology in 2015, by Dr D. P.

Al-Adra of the University of Edmonton, Canada and others.[2] These data showed

a median overall survival of 15.5 months and treatment response rate of 28% in

patients treated with SIRT.

    In addition, the new ESMO guidelines on biliary cancers call special

attention to a subset of studies in the pooled SIRT analysis, stating that

"importantly, 7/73 (10%) patients in three selected studies were converted to

resectable disease, highlighting the importance of reassessment of patients in

the multidisciplinary team in the event of a good response to any treatment."

    Dr David N. Cade, Chief Medical Officer of Sirtex Medical Limited, said

that "We are delighted to see SIR-Spheres(R) Y-90 resin microspheres cited in

the new ESMO guidelines as an important post-chemotherapy option for patients

with locally advanced or metastatic iCCA, given no current standard of care

exists beyond first-line treatment with cisplatin and gemcitabine chemotherapy

in these patients. We believe that these are the first international clinical

guidelines to indicate SIRT as a treatment option for patients with iCCA."

    Most iCCA patients are diagnosed relatively late in the course of their

disease, and therefore are not immediately eligible for potentially curative

surgical resection. The fact that even a small proportion of these patients may

become surgically resectable after chemotherapy suggests that SIRT may offer

real hope for them.

    Dr Cade added that, "The relatively favourable outcomes for iCCA patients

treated using SIR-Spheres Y-90 resin microspheres after having already failed

chemotherapy have encouraged Sirtex to conduct a randomised controlled study in

the setting of first-line treatment for iCCA. The SIRT in Cholangiocarcinoma

(SIRCCA) study is examining the role of SIR-Spheres Y-90 resin microspheres

followed by the standard-of-care first-line chemotherapy for iCCA, compared to

chemotherapy alone.

    SIRCCA is being conducted in some 30 centres in Australia and several

European countries, including Belgium, France, Germany, Italy, Spain, The

Netherlands and UK.

    About Cholangiocarcinoma

    Although relatively rare, cholangiocarcinoma is the second-most common form

of primary liver cancer.[3] The most common form of primary liver cancer, HCC

or hepatocellular carcinoma, is the world's second-largest cause of cancer

deaths.[4]

    In the westernized countries of Europe, North America and Australasia,

incidence rates are low, with estimates ranging from 0.3 to 3.5 cases per

100,000 people annually. However, incidence rates are much higher in parts of

the world where parasitic liver fluke infections are common, which includes

Thailand, China and Korea. Northeast Thailand has the highest rate of

cholangiocarcinoma in the world, 90 cases per 100,000 people each year.[1]

    Other than liver fluke infection, cholangiocarcinoma can be caused by

chronic damage to the liver or bile duct, such as chronic inflammation (primary

sclerosing cholangitis, or PSC), bile-filled choledochal cysts and bile duct

stones.[5]

    Surgical resection of the cancerous tissue can represent a definitive cure

for cholangiocarcinoma that is diagnosed early. For those patients diagnosed

with later-stage disease, chemotherapy with cisplatin and gemcitabine (a

combination referred to as CIS-GEM) is the initial treatment of choice, with

SIRT now regarded as the next line of therapy.

    The intrahepatic form of cholangiocarcinoma (iCCA) covered in the new ESMO

guideline is one of three types of the disease that physicians differentiate,

primarily based on where the disease is located within the target organ. The

other two forms are perihilar cholangiocarcinoma (pCCA), and distal

cholangiocarcinoma (dCCA).[1]

    About The Selective Internal Radiation Therapy in Cholangiocarcinoma

(SIRCCA) Study

    SIRCCA, which will begin recruiting patients in late 2016, is a Phase II

randomised clinical study for patients with intrahepatic cholangiocarcinoma

(iCCA), a form of primary liver cancer that originates in the bile duct, a

branching network of thin tubes that start in the segments of the liver and

deliver fat-digesting bile to the small intestine. The SIRCCA study, sponsored

by Sirtex, is designed to compare the effects of treating iCCA patients using

the sequence of SIR-Spheres Y-90 resin microspheres followed by the

standard-of-care cisplatin plus gemcitabine (CIS-GEM) chemotherapy versus

CIS-GEM chemotherapy alone.

    The key eligibility patient criteria are unresectable intrahepatic

cholangiocarcinoma that is confined to the liver or predominately in the liver,

who have not previously received chemotherapy, with adequate blood, liver and

kidney function, and in good overall heath (defined as ECOG performance status

0 or 1; ECOG 0 is fully active, while ECOG 1 is restricted in physically

strenuous activity but able to carry out light house work or office work).

    SIRCCA will enroll 180 patients at more than 30 treatment centres in,

Australia and several European countries, including Belgium, France, Germany,

Italy, Spain, The Netherlands and UK. The principal investigators of SIRCCA are

Dr Harpreet Wasan, Hammersmith Hospital, Imperial College, London UK and Prof.

Jordi Bruix, Barcelona Clinic, Spain. More information about SIRCCA can be

found at https://clinicaltrials.gov/ct2/show/NCT02807181.

    About SIRT

    Selective Internal Radiation Therapy (SIRT), also known as

radioembolisation, is a liver-directed therapy for inoperable liver tumours,

which is why the new ESMO guideline specifies its use for cholangiocarcinoma

within the liver.[1] SIRT is administered by a specially trained Interventional

Radiologist. A microcatheter is used to deliver millions of radioactive

microspheres into the hepatic artery, where they are carried into the

arterioles and selectively lodge in the tumour microvasculature.

    About SIR-Spheres Y-90 resin microspheres

    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 tumors from primary colorectal cancer with adjuvant intra-hepatic artery

chemotherapy (IHAC) of FUDR (Floxuridine).

    About Sirtex

    Sirtex Medical Limited (ASX: SRX) is an Australian-based global healthcare

business working to improve treatment outcomes in people with cancer. Our

current lead product, SIR-Spheres Y-90 resin microspheres, is a targeted

radiation therapy for liver cancer. Approximately 67,000 doses have been

supplied to treat patients with liver cancer at more than 1,000 medical centres

in over 40 countries. For more information, please visit http://www.sirtex.com .

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

    References

     1) Valle JW, Borbath I, Khan SA, Huguet F, Gruenberger T & Arnold D, On

behalf of the ESMO Guidelines Committee. Biliary cancer: ESMO Clinical Practice

Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 2016; 27

(Suppl 5): v28-v37.

     2) Al-Adra DP, Gill RS, Axford SJ et al. Treatment of unresectable

intrahepatic cholangiocarcinoma with yttrium-90 radioembolization: a systematic

review and pooled analysis. Eur J Surg Oncol 2015; 41: 120-127.

     3) Tyson GL, El-Serag HB. Risk Factors of Cholangiocarcinoma. J Hepatol

2011; 54: 173-184.

     4) Ferlay J, Soerjomataram I, Ervik M 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 10/October/2016.

     5) NHS Choices. Bile Duct Cancer (cholangiocarcinoma):

http://www.nhs.uk/Conditions/Cancer-of-the-bile-duct/Pages/Introduction.aspx,

accessed on 10/October/2016.

    410-EUA-1016

Source: Sirtex Medical Limited