InSIRT trial: Single-center phase II study of yttrium-90 radioactive resin microspheres in the treatment of liver-predominant metastatic colorectal adenocarcinoma after failure of first-line combination chemotherapy.

Abstract

685 Background: Liver metastases develop in half of colorectal cancer (CRC) cases and once metastatic ~90% die due to consequences from the hepatic metastases. We are evaluating the aggressive management of liver metastases through the incorporation of selective internal radiation therapy (SIRT) using yttrium-90 radioactive microspheres after evidence of progressive disease following first-line FOLFOX ± bevacizumab. Optimal timing for microsphere treatment relative to chemotherapy is not clearly established. We present preliminary data of a phase II study evaluating tumor response rates to SIRT following FOLFOX ± bevacizumab and prior to FOLFIRI. Methods: Subjects with predominant hepatic metastatic CRC despite first-line FOLFOX based therapy ± bevacizumab are eligible. Interventional radiology and nuclear medicine assess the liver lesions and the subject receives SIRT followed by second-line FOLFIRI (without bevacizumab) 4-6 weeks after the final SIRT. The primary objective is PFS at 6 mos and secondary objectives include: OS, tumor response rates, and toxicity. Results: To date, 8 metastatic CRC subjects have been treated and 9 subjects enrolled (goal 30 subjects). One subject was withdrawn due to progressive lung metastases. 4 of 8 subjects (50%) achieved PFS at 6 mos and average TTP is 6.7 mos (0.7-17.3 mos). Overall treatment has been well tolerated, but one possible study related SAE of liver failure occurred (subject 8). The OS endpoint has not been achieved. Conclusions: Historically, second-line FOLFIRI has achieved a 2.5 mos median PFS. In 8 subjects with liver predominant metastatic CRC, we have observed 50% PFS at 6 mos. These encouraging results demonstrate the utility of an innovative direct approach to metastatic CRC after failure of first-line combination chemotherapy. [Table: see text]