High Hopes for SIRFLOX: An Interview With David Liu, MD

David Liu, MD, is an interventional radiologist at Vancouver General Hospital and the BC Cancer Agency based in Vancouver, British Columbia, Canada. He is also an associate clinical professor at the University of British Columbia with adjunct appointments in surgery and medical oncology. Dr. Liu has been involved in the interpretation as well as the improvement in communication and understanding of the results from the SIRFLOX trial, a randomized phase 3 trial comparing first-line mFOLFOX6 ± bevacizumab vs mFOLFOX6 + selective internal radiation therapy (SIRT) ± bevacizumab in patients with metastatic colorectal cancer (mCRC).

IO360: What was the design and aim of SIRFLOX?

Liu: The SIRFLOX trial is a very interesting trial on a number of different levels. First, it’s the largest phase 3 clinical trial looking at first time treatment for mCRC with an interventional technique. As a result of this, the trial itself was formatted for two dimensions. The primary outcomes measure was actually progression free survival (PFS) at any site. The secondary measures included overall survival, as well as liver-specific PFS, toxicity, and quality of life. The trial was formatted to be able to speak to the medical oncology community about the utility of interventional techniques and specifically SIR-Spheres yttrium 90 (Y90) microspheres in the setting of metastatic colorectal carcinoma. 

One of the most exciting parts about this trial was that it was accepted for oral abstract presentation at the annual meeting of the American Society of Clinical Oncology (ASCO). What this means is that it is presented as an almost plenary session with 3,000 to 4,000 medical oncologists present at the time of the presentation of the data. Now, the data as they were presented are a little more complex, however as you will see in subsequent discussions following, it is interpretable and it is understandable. Essentially what it demonstrated is that when we look at overall progression free survival that there was no difference between the use of Y90 resin microspheres with chemotherapy as compared to chemotherapy alone. 

IO360: What are some of the most important results?

Liu: One of the reasons that the primary endpoint is such a challenge is because of the makeup of the population that was recruited in the study. Forty percent of the study presented with extra hepatic disease upon enrollment. In other words, 40% of people had disease outside of the liver and 45% of patients actually had their primaries intact, so they actually had their initial tumors prior to spreading to the liver intact, so there is automatically a bias for the populations to continue to progress outside of the liver. The more interesting finding was actually one of the secondary outcome measures, which was liver-specific PFS, and that was a very dramatic and substantial difference. There was a 7.9 month difference, or 7.9 month improvement, in PFS with the interventional arm using Y90 resin microspheres as compared to chemotherapy alone. What that’s telling us is that there is a very strong signal in liver response using Y90 resin microspheres and contemporary chemotherapy. 

IO360: What further investigation is being done?

Liu: One of the things we’re looking forward to is another secondary outcome measure, the ultimate measure, which is overall survival. The beauty of the SIRFLOX trial is that it was designed and engineered to be part of a series of three clinical trials, that being SIRFLOX, FOXFIRE, and FOXFIRE Global, to look at overall survival. When you put these three trials together, the actual population becomes over 1100 patients, and that becomes one of the largest clinical in medical oncology, not to mention interventional radiology and interventional oncology. 

There’s a lot of information to look forward to and although the SIRFLOX primary outcome measure did not reach its primary endpoint, we’re still encouraged by the signal of the liver-specific disease. The reason why we’re encouraged by that is because when we look at different types of interventional techniques for cytoreduction, or reduction of tumor burden within the liver, across the board there’s an improvement in survival. When we look at surgical resection, we know by default that this is the standard for cytoreductive therapy, or liver-directed therapy. When we look at ablation, as presented in the CLOCC trial, which was also presented at ASCO 2015 in the same session, we see that there’s long-standing and robust improvement in survival even in the setting of unresectable disease utilizing cytoreductive strategies. When we take a look at Y90 resin microspheres in the setting of chemosalvage or chemorefractory patients, there is also demonstrated to be an improvement in PFS and survival has also been demonstrated to be substantially better in patients receiving yttrium 90 resin microspheres and chemotherapy in an older-generation chemotherapy too. 

If we actually look at the vectors and the plots and we see how all of this converges, I think it’s going to be a very exciting time in 2017 when we have that overall survival data that’s going to be a conglomerate of 3 major clinical trials that are currently active in this area. 

Related:

• Video: David Liu, MD, Discusses SIRFLOX
• SIRFLOX Data Show Mixed Results for Survival
• New SIRFLOX Study Data Presented at World Congress of Gastrointestinal Cancer

Suggested citation: Ford J. High hopes for SIRFLOX: an interview with David Liu, MD. Intervent Oncol 360. 2016;4(1):E14-E15.