Randomized Controlled Trial of Radioactive Resin Microspheres Demonstrates Significant Delay in Progression of Disease in Patients With Colorectal Cancer Liver Metastases who Have Exhausted Chemotherapy

ORLANDO, Florida - The time to progression of disease in patients with colorectal cancer liver metastases who have exhausted all chemotherapy options can be more than doubled through the use of radioactive resin microspheres, according to the results of a prospective randomized controlled trial presented at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO).[1] The multicenter phase III study compared the use of 5-fluorouracil (5FU) alone to 5FU plus 90Y resin microspheres (SIR-Spheres; Sirtex Medical, Sydney) and was conducted by a collaboration of university hospitals in Belgium.

“Patients with colorectal cancer liver metastases who are resistant or intolerant of chemotherapy should be considered for salvage therapy using 90Y resin microspheres combined with 5FU-based chemotherapy,” said Dr Alain Hendlisz, Head of Digestive Oncology and Gastroenterology at Institut Jules Bordet Université Libre de Bruxelles, Brussels, Belgium, and principal investigator of the study. “The addition of 90Y resin microspheres to systemic 5FU significantly prolonged the time to progression compared with 5FU alone, more than doubling the interval before disease recurrence in the liver or anywhere in the body, and was well tolerated by patients who had already received many previous lines of chemotherapy.”

The median time to progression of liver disease - the primary endpoint of the study - increased from 2.1 months with 5FU alone to 5.5 months with 5FU plus 90Y resin microspheres (hazard ratio 0.38; 95% confidence interval [CI] 0.20-0.72; p=0.003) whilst the median time to progression of disease anywhere in the body was 2.1 vs. 4.6 months, respectively (hazard ratio 0.51; 95% CI 0.28-0.94; p=0.03). The proportion of patients with disease control following the combination treatment was also increased significantly from 35% to 85%, respectively (p=0.001), with one patient (5%) receiving 5FU plus 90Y resin microspheres having a sufficiently large reduction in tumor size to permit potentially curative surgical resection of the remaining disease.

All 44 patients in the study had colorectal cancer restricted to the liver, a median age of 62 (range 45 to 91 years) and had failed or could not tolerate multiple prior lines of standard-of-care chemotherapy comprising 5FU, oxaliplatin, irinotecan and available biologic agents.

Following disease progression, 10 patients (43.5%) in the 5FU-only arm subsequently crossed over to receive 90Y resin microspheres as a salvage therapy, and so overall survival was extended in both treatment arms by the targeted treatment of liver tumors. Overall, there was 2.5 months’ difference in the median survival (7.4 versus 9.9 months) between the 5FU and 5FU plus 90Y resin microspheres arms, respectively (hazard ratio 0.92; p=0.80). Treatment with 5FU plus 90Y resin microspheres was well tolerated, with significantly more patients experiencing a serious adverse event in the 5FU-only control arm (4% vs. 35%, respectively; p=0.02).

“The encouraging results of this randomized trial confirm the findings from single-arm and retrospective studies of 90Y resin microspheres that have reported median overall survivals in the order of 10 to 13 months when used alone as salvage therapy for patients with liver-dominant metastatic colorectal cancer who have exhausted all chemotherapy options,” said Dr Hendlisz.[2-4] “Small randomized controlled trials have also demonstrated significant benefits of using 90Y resin microspheres earlier in the treatment paradigm and our objective now is to investigate whether the addition of 90Y resin microspheres to current first-line standard-of-care chemotherapy could further improve the outcomes for patients with this disease.”[5,6]

The trial was conducted at the Institut Jules Bordet Université Libre de Bruxelles, Brussels, Universitair Ziekenhuis Gent, Ghent, and University Hospitals Leuven, Leuven, with collaboration from clinicians at the Hôpital Universitaire Erasme in Brussels. The study was supported by Sirtex Medical through the provision of 90Y resin microspheres and a research grant.

References

1. Van den Eynde M, Hendlisz A, Peeters M et al. Prospective randomized study comparing intra-arterial injection of yttrium-90 resin microspheres with protracted IV 5FU continuous infusion versus IV 5FU continuous infusion alone for patients with liver-limited metastatic colorectal cancer refractory to standard chemotherapy. 45th ASCO Annual Meeting Proceedings Journal of Clinical Oncology 2009; 27 (Suppl 7s): Abstract 4096.

2. Cosimelli M, Mancini R, Carpanese L et al. Clinical safety and efficacy of 90yttrium resin microspheres alone in unresectable, heavily pre-treated colorectal liver metastases: results of a phase II trial. ASCO Annual Meeting Proceedings Journal of Clinical Oncology 2008; 26 (May 20 Supplement): Abs. 4078.

3. Jakobs TF, Hoffmann RT, Dehm K et al. Hepatic yttrium-90 radioembolization of chemotherapy-refractory colorectal cancer liver metastases. Journal of Vascular and Interventional Radiology 2008; 19: 1187-1195.

4. Kennedy A, Coldwell D, Nutting C et al. Resin 90Y-microsphere brachytherapy for unresectable colorectal metastases: modern USA experience. Int J Radiation Oncology Biol Phys 2006; 65: 412-425.

5. van Hazel G, Blackwell A, Anderson J et al. Randomised phase 2 trial of SIR-Spheres plus fluorouracil/ leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer. Journal of Surgical Oncology 2004; 88: 78-85.

6. FOLFOX plus SIR-Spheres microspheres versus FOLFOX Alone in patients with liver mets from primary colorectal cancer (SIRFLOX). clinicaltrials.gov/ct2/show/NCT00724503

Source: Ruder Finn (France)

For further information, please contact: Mai Tran, Ruder Finn Paris; mob: +33-6-64-74-70-80 mtran at ruderfinn.fr