SIRT Suggested for Patients With Liver-Dominant CRC in Updated NCCN Guidelines

Kevin Richardson

Kevin Richardson

Selective internal radiation therapy (SIRT) using yttrium 90 (Y-90) microspheres has been recommended for selected patients with chemotherapy-resistant or refractory metastatic colorectal cancer (mCRC) with liver metastases in an update to the NCCN guidelines for colon cancer and rectal cancer.

SIRT, or radioembolization, using Y-90 can be administered to the liver tumors in either glass matrix or resin microspheres. The FDA has approved the use of SIR-Spheres to direct Y-90 resin microspheres in patients with mCRC with liver metastases.

In the guidelines, the authors noted that the panel members had all agreed that SIRT was an option in select patients for treating liver metastases, giving the treatment a category 2A recommendation. “The 2A designation represents a very important milestone for SIR-Spheres resin microspheres and provides further validation for the role of our medical device as an important treatment option for unresectable, liver-dominant metastatic colorectal cancer,” Kevin Richardson, CEO of Sirtex Americas, said in a statement.

The NCCN recommendation was partly based off of the phase III SIRFLOX trial which studied fluorouracil, leucovorin, and oxaliplatin (FOLFOX)-based chemotherapy (+/- bevacizumab) with or without SIR-Spheres as a first-line treatment in 530 patients with liver-only or liver-dominant mCRC.¹

Although the primary endpoint, progression-free survival (PFS) at any site, was not met in the trial (10.2 months in the control vs 10.7 months with SIRT [HR, 0.93; 95% CI, 0.77-1.12;P= .43]), PFS in the liver was significantly extended with SIRT (12.6 months control vs 20.5 months SIRT [HR: 0.69; 95% CI 0.55-0.90;P= .002]).

The objective response rate in the liver was also significantly improved with SIRT treatment in the SIRFLOX trial (68.8% control vs 78.7% SIRT;P= .042), as was the complete response rate (1.9% vs 6.0%;P= .020) and first progression only in the liver (77% vs 52.4%;P<.001).

&ldquo;We also have positive signals in the first-line setting through the results to date of the pivotal SIRFLOX study and eagerly anticipate the overall survival results in more than 1,100 patients from the SIRFLOX, FOXFIRE, and FOXFIRE Global studies, which we expect to be available in the first half of 2017,&rdquo; said Richardson.

The NCCN recommendation was also, in part, based off of the MORE study, which helped to assure the safety and clinical benefit of SIRT.

The MORE study examined 606 patients with mCRC and liver-dominant metastases treated with SIRT.²The most common adverse events experienced in the trial were fatigue (43.7%), abdominal pain (39.3%), nausea (28.4%), and vomiting (10.6%), most of which were only grade 1/2 and managed with medication. Patients experienced a median overall survival (OS) of 9.6 months with SIRT, and those without any extrahepatic metastases demonstrated a median OS of 12.1 months (P<.001). OS rates were increased in patients receiving SIRT in the second-line over those receiving SIRT in the third- or fourth-line (13 months, 9 months, and 8.1 months, respectively).

&ldquo;Clinical research has shown that SIRT brings patients with colorectal liver metastases improved and prolonged quality of life,&rdquo; said lead investigator of the MORE study, Andrew S. Kennedy, MD, director of Radiation Oncology Research at Sarah Cannon Research Institute. &ldquo;We look forward to expanding access to this outpatient procedure, which has demonstrated minimal side effects, to improve outcomes for this population of patients and advance the standard of care.&rdquo;

References:

1. van Hazel GA, Heinemann V, Sharma NK et al. SIRFLOX: Randomized Phase III trial comparing first-line mFOLFOX6 (plus or minus bevacizumab) plus selective internal radiation therapy in patients with metastatic colorectal cancer.J Clin Oncol. 2016;34:1723—1731.
2. Kennedy AS, Ball D, Cohen SJ et al. Multicenter evaluation of the safety and efficacy of radioembolization in patients with unresectable colorectal liver metastases selected as candidates for (90)Y resin microspheres.J Gastrointest Oncol.2015;6(2):134—142.