Studies Support Sirtex SIR-Spheres for Treatment of Liver Cancer Tumors

March 27, 2012—Two studies were recently presented that support radioembolization (selective internal radiation therapy [SIRT]) using yttrium-90 microspheres (SIR-Spheres, Sirtex Medical, Inc., Woburn, MA) for treating cancers of the liver.

At the Society of Interventional Radiology's annual scientific meeting in San Francisco, Constantinos T. Sofocleous, MD, presented data demonstrating that SIRT using SIR-Spheres is safe and provides clinical benefit for patients with colon cancer liver metastases who have previously undergone liver-directed and systemic chemotherapy.

At the Society of Surgical Oncology's annual Cancer Symposium in Orlando, Florida, Prof. Lourens Bester, MD, presented findings from a large comparative multicenter study of SIRT that demonstrated a significantly prolonged survival benefit following the use of SIR-Spheres in patients with treatment-refractory liver tumors from colorectal and other cancers.

According to Sirtex, SIRT is a novel technology for treating inoperable liver cancer in which millions of radioactive SIR-Spheres are infused via catheter into the liver, where they selectively target liver tumors with a dose of internal radiation that is up to 40 times higher than conventional radiotherapy while sparing healthy tissue. The company stated that clinical trials have confirmed that patients with metastatic colorectal cancer who are treated with SIR-Spheres have response rates that are higher than with other forms of treatment, resulting in increased life expectancy, greater periods without tumor activity, and improved quality of life. SIR-Spheres are approved for use in the United States, the European Union, and Australia, advised Sirtex.

At the San Francisco meeting, Dr. Sofocleous detailed the findings from a prospective single-center clinical study that assessed the safety, dose-limiting toxicities, and maximum tolerated dose of SIR-Spheres in a population of patients whose cancer had progressed despite hepatic arterial and systemic chemotherapy treatments.

During the 2-year period from September 2009 to September 2011, 19 patients received SIR-Spheres in three escalating dose levels. The first group received 70%, the second group received 85%, and the third group received 100% of their specific calculated dose.

The investigators found that common side effects of the SIR-Spheres were mild-to-moderate (grade 1 or 2) fatigue and mild (grade 1) fever, which were self-limiting and transient. One patient experienced grade 3 nausea and pain, and two patients had elevated bilirubin levels, which were attributed to progressive disease.

Evaluations at 4 to 8 weeks after treatment showed 12 patients (65%) with stable disease and five patients (29.4%) with disease progression. Median progression-free and overall survival times were 6 months (95% confidence interval, 3.2–9.7) and 16 months (95% confidence interval, 5.8–17.6), respectively. All patients underwent further chemotherapy, and nine patients received further hepatic artery infusion therapy. Furthermore, four patients had a decrease in carcinoembryonic antigen.

The investigators concluded that it is safe to administer the entire dose of SIR-Spheres in patients with colon cancer metastases who progressed despite previous pump and systemic chemotherapy.

“This study helps to confirm that we need to identify more effective treatment options for patients with colorectal liver metastases,” commented Dr. Sofocleous. “These results have met our expectations regarding safety of SIRT in heavily pretreated patients with good liver functions.”

At the Orlando symposium, Prof. Bester presented findings from an evaluation of 463 patients with chemotherapy-refractory liver-dominant tumors. He reported, “Radioembolization is associated with a significantly improved and clinically meaningful survival benefit. Whilst confounding factors may play a role, offering this treatment may confer the best prognosis for these patients.”

Prof. Bester serves as Director of Radiology at St. Vincent's Hospital in Sydney, Australia, which is also the home of Sirtex's global headquarters.

According to a statement by St. Vincent's Hospital, the aim of the study was to compare the outcomes of patients with liver tumors treated using radioembolization with patients receiving standard or best supportive care alone in the setting of treatment-refractory disease. All patients had chemotherapy-refractory liver-dominant tumors with radiologically confirmed progression and were no longer qualified for other treatment modalities such as resection, ablation, or chemoembolization.

The study excluded any patients with extensive extrahepatic metastases, symptoms that confined them to bed rest for more than 50% of the waking hours (Eastern Cooperative Oncology Group performance status > 2), excessive liver tumor burden (> 75% of liver replaced by tumor), and/or compromised residual liver function.

Of the 463 patients who underwent initial evaluation for radioembolization, 63 patients were considered unsuitable because of hepatic arterial anatomy that could not be corrected and that could otherwise have led to complications; extensive hepatopulmonary shunting between the liver and lungs, which raised the potential for excess radiation exposure to the lungs (> 30 Gy); or reasons relating to patient consent, such as a preference for another treatment option.

“The patients who were unsuitable for radioembolization were referred back to their treating physician for conservative treatment or continued supportive care,” explained Prof. Bester. “This group was unlikely to represent patients with more advanced disease and was consequently used as a standard care comparison cohort.”

The investigators found that among the 251 patients with colorectal liver metastases, median survival in the 220 patients treated with SIR-Spheres was 11.6 months compared to 6.6 months for the 31 patients who received standard or best supportive care (P = .021). In 212 patients with liver tumors from other cancers, including cholangiocarcinoma (41), neuroendocrine (40), hepatocellular carcinoma (27), pancreatic (13), breast (11), gastric (9), and other cancers (71), median survival was 9.5 months in the 180 patients treated with SIR-Spheres versus 2.6 months in 32 patients who received standard or best supportive care (P = .013).

Prof. Bester commented, “The significant improvement in overall survival in this study confirm the benefits demonstrated in two previous but smaller comparative studies that were performed in patients with treatment-refractory colorectal liver metastases, notably the multicenter phase III randomized controlled trial conducted by Hendlisz and colleagues in Belgium and the matched pair analysis by Seidensticker and colleagues from Magdeburg, Germany, which reported median survivals of 10 and 8.3 months, respectively.”

St. Vincent's Hospital noted that two large international randomized controlled trials are underway to evaluate the effectiveness of adding radioembolization using SIR-Spheres to first-line chemotherapy in order to assess whether this treatment should be used as an early intervention in the treatment of patients with colorectal cancer liver metastases. In addition, three large randomized controlled trials are evaluating radioembolization using SIR-Spheres for hepatocellular carcinoma.