From FOXFIRE to the Future: What Recently Published Studies Mean for IO

dan brownIn this interview with Interventional Oncology 360, Daniel Brown, MD, FSIR, chief of interventional oncology at Vanderbilt University, discusses recent changes to his practice. He also comments on the results of the FOXFIRE Global study and how results from future studies may lead to a paradigm shift for interventional oncology. Dr. Brown will be a faculty member at the 2018 Symposium on Clinical Interventional Oncology (CIO) on February 3-4, 2018 in Hollywood, Florida.

What changes have you made recently to your practice, and what led to those changes?

We try to be evidence based in our decision making. Some recently published studies can help direct care in interventional oncology. One area of interest is portal vein thrombosis with hepatocellular carcinoma (HCC). In people with good performance status, we’re definitely using more Y90 in that space. 

There’s been some debate about first-line sorafenib versus arterial therapy in advanced (Barcelona Clinic Liver Cancer C) HCC. In our practice, we tend to use more Y90 for first line and then use sorafenib afterwards if necessary. The SARAH and the SIRveNIB studies suggest that we should be strongly considering Y90 for BCLC C disease, because radioembolization has less toxicity than sorafenib while maintaining similar survival time. There are also ongoing trials to determine whether combining arterial and biologic therapies up front is a good idea for advanced HCC. We don’t know the answer to that question yet because the data have not been published. However, combined therapy might be promising, especially because the BCLC criteria have only really focused on sorafenib for BCLC type C disease.

Are there any other recently published studies with significant results?

Another big study that was recently published is the FOXFIRE Global study, which showed that adding Y90 first line to standard colorectal chemotherapy did not improve overall survival.

These results were honestly a bit disappointing, but they shouldn’t be interpreted to mean that Y90 does not have benefit for patients with colorectal cancer. To me, this trial means specifically that using Y90 as an integral component of first-line chemotherapy is not beneficial.

We evaluate colorectal chemotherapy by lines of therapy. First-line therapy is typically FOLFOX or FOLFIRI, plus or minus biologics, and second line is whichever regimen wasn’t administered in first line. There is an ongoing trial, the EPOCH study, that is combining second-line chemotherapy with glass microspheres compared to chemotherapy alone. Beyond second-line therapy, salvage therapy with radioembolization is not only a possibility, but it is also the greatest use of Y90 in patients with colorectal cancer. 

Although there may be some pushback and questions after FOXFIRE, a failed first-line trial does not mean there is no use for the therapy. Rather, it means that the therapy is not preferable as an up front, first-line agent. This factor is important to keep in mind when having discussions and answering questions from colleagues in other specialties. When we do research, we want to clearly define where benefit is and where it is not. There is no perfect solution that’s appropriate anywhere in the therapy time line.

I’m hoping that as the Radiation-Emitting SIR-Spheres in Non-Resectable (RESIN) Liver Tumor Patient Registry we’re running out of Vanderbilt matures, we’ll find some signal in the noise, and find actionable areas for prospective research down the road.

In colorectal cancer, one of the areas that may benefit from the registry is finding signal to noise in salvage situations using Y90 with different biologic agents. There’s a lot of opportunity in interventional oncology to do good research and find ways to improve survival. By the time patients are at third-line therapy or further, survival in those trials is always less than a year. We want to find a way to improve that survival curve and extend life duration and quality.

A subset analysis suggested that treatment with selective internal radiotherapy might be beneficial for patients with right-sided colorectal tumors. What are your thoughts on this interpretation?

Right-sided vs left-sided colon cancer is a hot topic. The primary endpoint of the FOXFIRE Global study was overall survival, so I don’t think FOXFIRE demonstrates that we should be using Y90 first line in everybody with right-sided colon cancer. However, I think future prospective research focusing on right-sided vs left-sided cancers is of interest.

In general, how do you decide when it’s time to make a change in practice?

Prospective randomized trials are the gold standard, but prospective randomized trials in interventional radiology with significant data samples have been few and far between. That said, many areas of medicine have not been based on prospective data. Very significant procedures have been identified via retrospective reviews and then validated prospectively afterward. In that respect, interventional radiology and interventional oncology are similar to other specialties.

When treating patients with metastatic disease with liver-directed therapy, we typically use Y90 first rather than bland or chemoembolization because the recovery is so much easier. The Northwestern group has shown that quality of life (QOL) is better maintained after Y90 than chemoembolization in their prospective data looking at QOL measures. These outcomes are consistent with our practice.

If we do bland embolization of neuroendocrine tumors, sometimes the patient is admitted for 2 or 3 days, and it’s a tough recovery. Additionally, when treating patients with neuroendocrine tumors, especially low-grade tumors, over time you’re probably going to use Y90 and bland embolization and chemoembolization because patients’ longer survival times allows them to receive multiple treatments. I prefer to start with Y90. Maintaining QOL is crucial.

Are there any areas of interventional oncology that are in need of more recent data?

Regarding metastatic disease, there haven’t been many recent studies published on good old-fashioned chemoembolization. Most of the recent publications on metastatic colorectal cancer and other tumors have been on Y90.

Drug-eluting beads have been static, but that doesn’t mean there is a problem. It just means that there haven’t been large studies examining drug-eluting beads with irinotecan for colorectal, for example.

What are you most excited about in terms of upcoming studies and the future or interventional oncology?

I’m hoping to see results from EPOCH, the second-line colorectal trial. Second-line chemotherapy for colorectal cancer does not have a tremendously good response rate, and I think there is a greater opportunity for success in second-line therapy than first-line. If the data are positive, treatment of second-line colorectal cancer would be significant for interventional oncology because it involves a much larger population than the HCC population, which is interventional oncology’s primary referral group is. If second-line colorectal treatment becomes a viable option, it would represent an enormous paradigm shift for interventional oncology.