Results of the PREMIERE Trial: An Interview With Riad Salem, MD

Editor's note: See related video here.

Riad Salem, MD, chief of interventional radiology at Northwestern University, spoke with Interventional Oncology 360 at the 41st annual scientific meeting of the Society for Interventional Radiology about results of a prospective randomized phase 2 study of chemoembolization vs radioembolization in hepatocellular carcinoma (the PREMIERE trial). 

IO360: Could you give us some background on the study?

Salem: The PREMIERE trial is a prospective randomized trial comparing chemoembolization and radioembolization in patients with hepatocellular carcinoma. It is the first randomized trial to be published that really addresses a question that people have asked for many years comparing 2 main regional local therapies, radioembolization and chemoembolization. The study was terminated early because of difficulty in enrollment, but we were still able to extract significant information from the study, probably sufficiently enough for people to implement the therapy in their clinical practice.

IO360: How many patients were enrolled?

Salem: We had 45 patients that were enrolled. The consort diagram talks about the screening and the eligibility so we had 179 people that were candidates for treatment over a 5-year period, but only 45 opted to be randomized. Patients in general don’t necessarily associate positive things with research, with clinical trials, or with computers telling them how they are going to be treated. So we only randomized 45 patients, 24 in the radioembolization arm and 21 in the chemoembolization arm. Again despite that moderate size study, we were able to extract meaningful information.

IO360: What results were you able to obtain?

Salem: When we closed the trial we had a blinded review of the results. The primary endpoint of the study was time to progression, that is, which treatment is better able to control the liver disease, and what we found by having a blinded review was that radioembolization was significantly better at controlling liver disease compared to chemoembolization. The time to progression in the chemoembolization arm was 6.4 months and the time to progression in the radio embolization arm was over 26 months. In fact, we hadn’t reached the median endpoint, so one was significantly better and we achieved a hazard ratio of .13 with a P value of .002, so highly significant, and 87% risk reduction of progression with radioembolization compared to chemoembolization.

IO360: How do you think this is going to affect IO practice in general?

Salem: That’s a good question. This was the trial — or at least the design of a trial — that people have wanted to see for many years. Because we are a cancer center where we perform a lot of chemoembolization and a lot of radioembolization, we are one of the few centers that actually could undertake this trial. However, we suffered from the real-life difficulties you see in comparative effectiveness analyses. Patients don’t want to be randomized. Patients want a specific therapy. Patients don’t like computers telling them what to do. 

But again, we were able to extract meaningful data, and at every time point in the Kaplan-Meier analysis, there is an 87% risk reduction of progression in the radioembolization group compared to chemoembolization. This is important. Transplant these days has a longer waiting list so you must be able to control disease, which means that you want the treatment that will maximize the ability to control disease. In our experience, this appears to be radioembolization.

IO360: Had a study like this been attempted before and couldn’t be enrolled? Is this the culmination of years of trying?

Salem: It’s the culmination of many things. For several years, people have preferred one treatment over another and it’s been fodder for debate. Which treatment is better? We at our center have been very systematic as to how to approach radioembolization. We described the safety aspects of it, the technical aspects of it, the applicability of it, the quality of life aspects, the long-term survival, the transplantation.  

Now, the difficulty in going beyond that and talking about overall survival is that many patients go on to other treatments after chemoembolization and radioembolization, so the survival outcome is confounded by alternate therapies. But again, for local control, Y90 outperforms chemoembolization, something that we are the first to now show. There are some other international studies that are starting, but I believe they had significant problems with enrollment because people are starting to see great results with the radioembolization and now no longer want to randomize to chemoembolization. I suspect once the data of our trial are published, they will have even more difficulty randomizing because of the results. 

IO360: So does this confirm what has anecdotally been observed in the IO community?

Salem: It depends on the side that you are on. If you are on the radioembolization side, sure it confirms and if you are on the other side, it probably builds a bit more skepticism because you don’t really believe it. But my answer to that is if you believe otherwise, do the randomized trial and disprove it. That’s how science works. So, we did this to the best of our abilities, enrolled these 45 patients, we have comprehensive data, and we are very excited about the results. Those in disbelief have the obligation to do a randomized study and refute our findings.

IO360: What do you think is the most important takeaway for IO clinicians about the study?

Salem: The most important point for an IO clinician is probably that you now have an outpatient treatment that will give you significantly improved time to progression and local disease control, maintaining quality of life, with the ability to potentially bridge you to transplantation because there is now a mandated wait time before transplant. A mandated wait time means you have to wait. It means you can’t undergo early expedited transplant so now you must think about the treatment that is more likely to control disease than not and, according to our study, that’s radioembolization. 

The other thing is that it does confirm what we have seen previously, that is the applicability in radiation lobectomy with downstaging and bridging to resection and radiation segmentectomy. In some cases, you can potentially cure the patient of their cancer without surgery. This is one of the nice things about this technology with its versatility, how it has broad applicability across multiple stages in patients with hepatocellular carcinoma.

Editor’s note: Dr. Salem reports consultancy to and research grants from BTG.

Suggested citation: Ford J. Results of the PREMIERE trial: an interview with Riad Salem, MD. Intervent Oncol 360. 2016;4(6):E112-E114.