This article is more than 5 years old. Information may no longer be current.

No overall improvement in mCRC PFS with Y-90 spheres, but liver-only metastases respond well

Radiation therapy using yttrium-90 resin microspheres combined with chemotherapy did not improve overall progression-free survival in patients with nonresectable metastatic colorectal cancer. However, the combination regimen did improve survival in patients with liver-only metastases, according to newly published data on the SIRFLOX study.

“This … added treatment benefit [in patients with liver-only metastases] represents a significant 31% reduction in the risk of tumor progression in the liver for patients treated with SIR-Spheres Y-90 resin microspheres,” Guy A. van Hazel, MD, clinical professor of medicine at the University of Western Australia in Perth, Australia, said in a press release. “Our new analyses focused on the impact of two important factors on this treatment benefit.”

Between October 2006 and April 2013, van Hazel and colleagues randomly assigned 530 chemotherapy-naive patients with non-resectable, liver-only or liver-dominant metastatic colorectal cancer (mCRC) to a regimen of either leucovorin, fluorouracil and oxaliplatin (mFOLFOX6) with or without Avastin (bevacizumab, Genetech; n = 263) or a regimen of mFOLFOX6 plus selective internal radiation therapy (SIRT) using SIR-Spheres Y-90 resin microspheres (yttrium-90 resin microspheres, Sirtex Medical Limited; n = 267) and one cycle of bevacizumab, until disease progression.

Although clinically insignificant, the researchers found that the overall response rate was lower among patients who did not receive Y-90 spheres treatment compared with those who did (68.1% vs. 76.4%; P = .113). The hepatic response rate was also lower in the non-Y-90 spheres group (68.8% vs. 78.7%; P = .042), with a complete response rate of 1.9% compared with 6% in the Y-90 spheres-treated group (P = .02).

Kaplan-Meier analysis showed the median overall progression-free survival (PFS) was lower in patients who did not undergo treatment with Y-90 spheres compared with patients who did (10.2 vs. 10.7 months; P = .429).

Among patients in the intention-to-treat (ITT) without bevacizumab cohort, the median liver PFS was lower in patients who did not undergo treatment with Y-90 spheres compared with patients who did (10.6 vs. 18.9 months; P = .028), as well as lower in patients with ITT to receive bevacizumab (12.7 vs. 21 months; P = .018).

The rate at which grade 3 adverse events occurred were similar among the two groups — higher in the patients who received Y-90 spheres treatment, but not significant (73.3% vs. 85.4%), according to the research.

Liver Metastases

The overall median liver PFS was lower in patients who did not undergo treatment with Y-90 spheres compared with patients who did (12.6 vs. 20.5 months; P = .002).

Of patients with liver-only metastases, the median liver PFS was lower in patients who did not undergo treatment with Y-90 spheres compared with patients who did (12.4 vs. 21.1; P = .003).

“Among the 318 patients with metastases that had spread only to the liver at the time they entered the study, median PFS in the liver was 21.1 months for those treated with SIR-Spheres plus chemotherapy, compared to 12.4 months for those treated with chemotherapy alone,” van Hazel said.

Van Hazel said in the release that this nearly 9-month improvement was significant (P = .003) and represents “a notable 36% reduction in the risk of tumor progression in the liver.”

Of patients with liver and extra-hepatic metastases, the median liver PFS was lower in patients who did not undergo treatment with Y-90 spheres compared with patients who did (12.6 vs. 16.7 months; P = 0.147).

“The clinical benefit of adding SIR-Spheres Y-90 resin microspheres to first-line chemotherapy appears to be independent of the use of bevacizumab,” van Hazel said.

Van Hazel concluded: “Even in the absence of a statistically significant improvement in progression-free survival at all sites, as was the case in SIRFLOX, and even as we await overall survival data from the combined 1,100-patient SIRFLOX, FOXFIRE and FOXFIRE Global studies in 2017, these new pre-planned subgroup findings for PFS in the liver should lead oncologists to consider adding SIR-Spheres Y-90 resin microspheres to first-line chemotherapy.” – by Melinda Stevens

Disclosures: Healio.com/Hepatology was unable to verify relevant financial disclosures at the time of publication.