SIRFLOX: Sirtex Microspheres Show Significant Improvement in Progression-Free Survival in Liver Cancer Treatment

 

May 30, 2015—Sirtex Medical Limited announced that data from the SIRFLOX study were presented by coprincipal investigator Peter Gibbs, MD, at the 2015 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Illinois. SIRFLOX is evaluating the benefits of adding liver-directed SIR-Spheres Y-90 resin microspheres to a current systemic chemotherapy for the first-line treatment of unresectable metastatic colorectal cancer (mCRC). Associate Professor Gibbs is Consultant Medical Oncologist at The Royal Melbourne Hospital in Melbourne, Australia.

In March, the company announced preliminary results from the trial and at that time advised that the primary endpoint of the SIRFLOX study was not achieved. The preliminary analysis showed that adding SIR-Spheres Y-90 resin microspheres to a current first-line systemic chemotherapy regimen for the treatment of nonresectable mCRC does not result in a statistically significant improvement in the overall progression-free survival, which measures progression of existing tumors and/or the development of new tumors in any organ or body site. However, the preliminary analysis showed that SIR-Spheres Y-90 resin microspheres did result in a statistically significant improvement in progression-free survival in the liver.

According to the company, the results of the 530-patient SIRFLOX randomized controlled study demonstrate new possibilities for combining radiation targeted at liver metastases with first-line systemic treatment of mCRC. SIR-Spheres Y-90 resin microspheres are used for selective internal radiation therapy (SIRT), or radioembolization, which targets high doses of radiation directly to liver tumors. The treatment consists of tens of millions of radioactive Y-90–coated resin particles delivered into the hepatic artery.

In Sirtex’s press release, Prof. Gibbs reported, “We found that while liver tumors began to grow again after a median of 12.6 months in patients with mCRC who received only first-line chemotherapy, those who also received first-line treatment with SIR-Spheres Y-90 resin microspheres had their liver tumors controlled for a median of 20.5 months. The additional 7.9 months of treatment benefit with the combined first-line SIRFLOX regimen was statistically significant, with a value of .002 and a hazard ratio of 0.69. This translates to a 31% reduction in the risk of tumor progression in the liver for patients treated with Y-90 resin microspheres.”

Prof. Gibbs continued, “This finding matters a great deal because the liver is almost invariably the organ where colorectal cancer spreads to first. While half the patients initially diagnosed with colorectal cancer survive thanks to surgical removal of the primary tumor before the disease has spread elsewhere in the body, liver metastases eventually cause the death of the majority of the remaining hundreds of thousands of patients each year whose tumors spread but are inoperable.”

Prof. Gibbs also reported that liver treatment response rates were significantly higher in patients who received Y-90 resin microspheres in combination with first-line chemotherapy, which consisted of a Folfox-based regimen, with or without the addition of bevacizumab. Prof. Gibbs stated, “We observed a hepatic response rate of 78.7% in this group, compared to 68.8% in the chemotherapy-only group. This was statistically significant, with a value of .042. Moreover, the rate of complete responses in the liver of SIRFLOX patients who received SIR-Spheres Y-90 resin microspheres, though relatively small at 6%, was more than three times higher than the 1.9% complete response rate among the chemotherapy-only patients. The statistical significance of this finding is very strong, with a value of .02.”

At a press conference after the ASCO presentation, SIRFLOX coprincipal investigator Prof. Guy van Hazel, MD, who is Clinical Professor of Medicine at the University of Western Australia in Perth, Australia, commented on the study’s findings. He stated, “SIRFLOX gives us the data to validate the first-line use of selective internal radiation therapy, or SIRT, with SIR-Spheres Y-90 resin microspheres in mCRC. Until now, we have not had a randomized clinical study large enough to provide level one evidence supporting first-line use of this treatment.”

Prof. van Hazel continued, “This step forward matters to medical oncologists and their patients, because until the development of Y-90 resin microspheres, there was essentially no place for radiation therapy in the treatment of liver tumors. There was never a question that radiation would work in the liver, but the problem of administering the radiation in a way that spared healthy liver tissue from its effects prevented it from being an ‘equal partner’ with surgery and chemotherapy in treating mCRC, as it is in almost all other forms of cancer.”

Also at the press conference, Principal European investigator Volker Heinemann, MD, commented, “Medical oncologists, particularly also at the community level, are only now beginning to recognize that treating liver metastases locally as well as systemically is a very important clinical consideration in the effective management of this difficult-to-treat cancer and may also open up the possibility of potentially curative liver surgery in some previously unresectable cases.”

Dr. Heinemann continued, “The effect of Y-90 resin microspheres on progression-free survival in the liver, as reported in the SIRFLOX study, is quite pronounced. Even in the absence of sufficient data to calculate an overall survival benefit or a significant finding for the primary endpoint of progression-free survival at any site, the outcome of SIRFLOX suggests that oncologists who treat mCRC may now wish to consider earlier use of Y-90 resin microspheres than is presently the case, certainly among those patients whose metastatic disease has been diagnosed primarily in the liver.” Dr. Heinemann is Director of the Comprehensive Cancer Center at the University of Munich in Munich, Germany. He added, “With SIRFLOX, the level one evidence is there for every medical oncologist to see and to evaluate in their practice.”

Navesh K. Sharma, MD, the principal US investigator of SIRFLOX, noted, “With 530 patients, SIRFLOX is the largest randomized trial ever conducted that combined an interventional radiology procedure with chemotherapy in oncology.”

“Physicians have been performing SIRT procedures with Y-90 resin microspheres in the United States and around the world for more than 10 years. We have always felt that this procedure was a unique approach to deliver large doses of radiation to liver tumors, targeted in a way that spares healthy liver tissue. It is important to observe that in SIRFLOX, the clinical benefit that was observed came with an acceptable level of adverse events from adding Y-90 resin microspheres to first-line chemotherapy in mCRC. Oncologists, especially radiation oncologists, have traditionally been very cautious of irradiating large liver volumes because of the adverse effects associated with such treatments. SIRFLOX has shown us, in an unbiased manner that not only can we deliver high doses of radiation to the liver safely with this approach, but also we can do so using concurrent chemotherapy. Concurrent chemoradiation has been one of the most effective ways to treat cancer in general, especially those of gastrointestinal origin.” Dr. Sharma is Assistant Professor of Radiation Oncology and Diagnostic/Interventional Radiology at the University of Maryland Medical Center in Baltimore, Maryland, which was the largest US clinical site for SIRFLOX.

The company advised that SIRFLOX is the first of a group of three studies assessing the results of adding SIR-Spheres Y-90 resin microspheres to first-line chemotherapy in the treatment of mCRC. The other studies are FOXFIRE, a clinical trial in the United Kingdom that completed enrollment in November 2014, and FOXFIRE Global, an international study that completed enrollment in January 2015. The results of the three studies, which together enrolled more than 1,100 mCRC patients, will be combined in a preplanned assessment of the overall survival benefit of adding SIR-Spheres Y-90 resin microspheres to first-line chemotherapy for mCRC. The combined results are expected in 2017.

The coprincipal investigators of FOXFIRE are Professor Ricky Sharma, MD, Clinical Senior Lecturer in Oncology at the University of Oxford in the United Kingdom, and Harpreet Wasan, MD, of Hammersmith Hospital and the Imperial College Trust in London, United Kingdom. Prof. Gibbs is the principal investigator of FOXFIRE Global.

SIR-Spheres Y-90 resin microspheres have received US Food and Drug Administration approval, European CE Mark approval, and Australian Therapeutic Goods Administration Conformity Assessment certification. In the United States, the microspheres are indicated for the treatment of nonresectable metastatic liver tumors from primary colorectal cancer in combination with intrahepatic artery chemotherapy using floxuridine. The device is approved for the treatment of inoperable liver tumors in Australia, the European Union, Argentina, Brazil, and several countries in Asia, such as India and Singapore, advised Sirtex Medical Limited.

 

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