Selective Internal Radiation Therapy Impacts Liver Metastases in Colorectal Cancer


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Peter Gibbs, MD

We saw a major impact on control of liver metastases with the addition of Y-90 resin microspheres to standard first-line systemic chemotherapy in patients with metastatic colorectal cancer limited to the liver or small-volume extrahepatic disease.

—Peter Gibbs, MD

A novel interventional approach to treating liver metastases associated with colorectal cancer improved control of liver metastases, according to the SIRFLOX study presented at the 2015 ASCO Annual Meeting.1

The addition of selective internal radiation therapy to first-line chemotherapy extended median progression-free survival in the liver by almost 8 months in patients with liver-dominant metastases, compared with the control arm, although outcomes in the overall population were not improved, according to Peter Gibbs, MD, of The Royal Melbourne and Western Hospitals in Melbourne, Australia.

SIRFLOX, which evaluated the benefit of yttrium-90 (Y-90) resin microspheres as an adjunct to chemotherapy, is the largest randomized controlled trial of an interventional radiology procedure to date, he said.

‘An Ongoing Impact’

 “Our key message is that we saw a major impact on control of liver metastases with the addition of Y-90 resin microspheres to standard first-line systemic chemotherapy in patients with metastatic colorectal cancer limited to the liver or small-volume extrahepatic disease,” revealed Dr. Gibbs.

“This finding matters a great deal,” he commented, “because the liver is typically the organ where colorectal cancer spreads to first…. Hopefully, this will translate to an improvement in overall survival.”

Selective internal radiation therapy, which is administered by an interventional radiologist, employs Y-90–labeled resin microspheres into the hepatic artery, releasing a single, large dose of radiation directly to the tumor.

“It’s the single dose which is important,” emphasized Dr. Gibbs. “Most treatments we use in medical oncology are repeat dosing every 2 to 3 weeks—often for many months at a time. Selective internal radiation therapy is important because it’s a one-off treatment that has an ongoing impact over a long period of time.”

SIRFLOX Trial Details

The prospective, open-label, randomized controlled SIRFLOX trial enrolled 530 chemotherapy-naive patients with nonresectable liver-only or liver-dominant metastatic colorectal cancer. The primary tumor had not been removed in about 45% of patients, and 40% had extrahepatic disease, either low volume lung or lymph node metastases.

Patients were randomized to receive either modified FOLFOX6 (folinic acid, fluorouracil, oxaliplatin) with or without bevacizumab (Avastin; n = 263) or the same treatment with selective internal radiation therapy administered once with cycle 1 or 2 with or without bevacizumab until disease progression (n = 267). The primary endpoint was overall progression-free survival in the intent-to-treat population.

Benefit Restricted to the Liver

The analysis of overall median progression-free survival showed no difference between the two arms. Median progression-free survival was 10.2 months in the control arm and 10.7 months with the addition of selective internal radiation therapy (P = .43). However, major changes were observed within the liver, Dr. Gibbs reported.

For patients with liver metastases, “with systemic therapy alone, the median progression-free survival was 12.6 months. With the addition of selective internal radiation therapy, this increased to 20.5 months, a difference of 7.9 months (hazard ratio = 0.69; P = .002),” he reported. “Another way of saying this, is we saw a 31% reduction in the risk of disease progression within the liver.”

The hepatic response rate was 78.7% in selective internal radiation therapy–treated patients, compared with 68.8% in controls (P = .042). Although this difference may appear to mean little clinically, Dr. Gibbs noted that the rate of complete responses in the liver of selective internal radiation therapy–treated patients (6.0%) was more than triple that of patients treated with chemotherapy alone (1.9%; P = .02).

Rates of hepatic resection were similar: 14.2% with selective internal radiation therapy and 13.7% with modified FOLFOX alone (P = .857).

Toxicity

Selective internal radiation therapy–treated patients experienced a greater number of grade ≥ 3 adverse events, especially neutropenia (40.7% vs 28.5%), febrile neutropenia (6.1% vs 1.9%), and thrombocytopenia (9.8% vs 2.6%). Selective internal radiation therapy–associated events included gastric or duodenal ulcer (3.7%), ascites (2.8%), hepatic failure (1.2%), and radiation hepatitis (0.8%).

“Adverse events had no negative impact on duration of systemic therapy and were acceptable and as predicted,” indicated Dr. Gibbs.

Future analyses will include subgroups of interest, particularly liver-only vs liver-dominant disease; the effect of bevacizumab; the depth of response; and quality of life. “Ultimately, however, we’re most interested in overall survival,” Dr. Gibbs said.

 Additional Commentary

At a press briefing, the principal U.S. investigator of the trial, Navesh K. Sharma, DO, PhD, Associate Professor in the Division of Radiation Oncology at Penn State Hershey Cancer Institute, Pennsylvania, commented: “SIRFLOX has shown us, in an unbiased manner, that not only can we deliver high doses of radiation to the liver safely with this approach, but we can do so using concurrent chemotherapy. Concurrent chemoradiation has been one of the most effective ways to treat cancer in general, especially those of gastrointestinal origin.”

Combined analysis of overall survival data from SIRFLOX and two additional trials (FOXFIRE and FOXFIRE Global) is expected in 2017. ■ 

Disclosure: Dr. Gibbs has received honoraria from Alchemia, Amgen, Bayer, Merck, Roche, and Sirtex Medical and research funding (institution) from Pfizer and Roche. Dr. Navesh Sharma has received honoraria from, consulted for, been on the speakers bureau of, and received travel expenses from Sirtex Medical.

Reference

1. Gibbs P, Heinemann V, Sharma NK, et al: SIRFLOX: Randomized phase III trial comparing first-line mFOLFOX6 ± bevacizumab versus mFOLFOX6 + selective internal radiation therapy ± bevacizumab in patients with metastatic colorectal cancer. 2015 ASCO Annual Meeting. Abstract 3502. Presented May 30, 2015.

 


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