Expert Anticipates Significant Shift in Clinical Practice for Liver-Dominant mCRC

Shannon Connelly
Published Online: Thursday, Nov 17, 2016

John L. Marshall, MD

John L. Marshall, MD

An overall survival (OS) analysis of 3 randomized controlled trials exploring Yttrium-90 (Y-90) resin microspheres may demonstrate noteworthy survival benefits for patients with liver-dominant metastatic colorectal cancer (mCRC) receiving first-line FOLFOX6 with or without bevacizumab (Avastin) plus Y-90 resin microspheres.

"If we see a survival advantage for these patients, I do think we’ll see a pretty significant shift in practice for these patients," said Marshall.

Past findings have shown that the addition of selective internal radiation therapy (SIRT), using Y-90 resin microspheres, to FOLFOX-based first-line chemotherapy in patients with liver-dominant mCRC did not improve overall progression-free survival (PFS). However, the regimen has been shown to achieve a significant improvement in median PFS in the liver, representing a reduction in risk of disease progression in the liver with no negative impact on duration of systemic therapy.

In an interview with OncLive, Marshall, chief, Division of Hematology and Oncology, Medstar Georgetown University Hospital, and director, Otto J. Ruesch Center for the Cure of Gastrointestinal Cancers, reviewed the findings from the phase III SIRFLOX trial, which was just the first of the 3 total trials investigating Y-90 resin microspheres. He also highlights the potential impact of the remaining 2 trials, FOXFIRE, and FOXFIRE Global, which will be combined with SIRFLOX for an overall survival analysis that will contain 1103 patients.

OncLive: Can you give an overview of your talk on liver-directed therapy?

Marshall: In colorectal cancer, particularly mCRC, we've created this new subclass of patients with liver-dominant or liver-only metastatic colon cancer, and we’ve got all sort of tools and new, effective ways of managing that. Part of my thinking is should we begin to carve out really its own pathway, its own strategy for these kind of patients.

I really spent most of the time reviewing the knowledge that we have today. We have this belief that we should be giving chemotherapy around the time of a surgery for liver metasteses, and yet there really is no solid evidence that says that chemotherapy will add benefit to patients. So it doesn’t really have an “adjuvant” effect like we’d like it to have, meaning more people are cured if you give chemo than just doing surgery, and there really has only been shown a minor improvement in progression-free survival (PFS). So I actually believe personally that this is a different kind of animal, the surgery either cures patients or you have to treat them to progression, or at least wait until mets recur and manage it that way, just thinking of metastatic disease.

But then there’s this other group that has come out and these are liver-dominant patients who can’t have surgery, and it is this group where we have some new, exciting tools. Traditionally, we’ve been giving just chemotherapy until they drop. Well now, we’ve got more and more evidence that liver-directed therapy, whether that is chemotherapy, or the latest bell and whistle is called Y-90, Yttrium-90, where that’s injected can treat and control liver metastases for an extended period of time.

The primary study that I reviewed was the SIRFLOX study, and SIRFLOX randomized patients between FOLFOX6 plus bevacizumab (Avastin) versus FOLFOX6 and bevacizumab plus Y-90, right at the beginning, not when we normally have been using it as a salvage refractory therapy, but right at the beginning during the first cycle.

What this showed was, at least in the liver, there was a 12-month versus 20-month liver PFS, so big piece of change, almost 8 months improved outcome in terms of liver-specific PFS. There are 2 other studies that are coming before the overall survival analysis will be done.

The trick or the problem with this is that in this study patients were included who had extrahepatic disease, so they could have small volume lung disease, lymph nodes, that sort of thing, so the overall PFS was no different between the 2 arms. We’ll figure this out – does liver-dominant disease deserve up-front liver-directed therapy or not? We’ll know in for sure in about a year when the overall analysis is done.


View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Cancer Summaries and Commentaries™: Update from Chicago: Advances in the Treatment and Management of CINVJul 26, 20171.5
Cancer Summaries and Commentaries™: Update from Chicago: Advances in the Treatment of Genitourinary CancersJul 28, 20171.5
Publication Bottom Border
Border Publication