Ghassan K. Abou-Alfa, MD: But another approach that we tried to do, if anything, is to see how we can enhance the TACE. And I have to say that I give the credit to Dr. Kudo, because he’s the first to do it. Teach us a little bit more about adding sorafenib to TACE.
Masatoshi Kudo, MD, PhD: Yes. Of course, we know the previous 5 trials combined TACE with targeted agents all failed. But the 3 trials with sorafenib all failed. But we looked at the data. The first one is a post-TACE trial conducted in Japan and Korea. The TTP was better in Korea, and the TTP in Japan was negative; not good. The difference is the treatment duration. In Korea, the sorafenib was continued 30 weeks, but in Japan, around 16 weeks. And another trial, the SPACE trial, they compared the Asian and non-Asian patients. And Asian patients received sorafenib more than 30 weeks, but in non-Asian patients, it was around 17 weeks. But the hazard ratio is better in Asia. That means longer treatment duration with sorafenib shows a better outcome. So, we define the new lesion as not the progression.
So, we create the definition of, specifically, TACE progression, and then that time to un-TACEable progression, so even though the new lesion appears, TACE can be performed superselectively. That means a new lesion does not mean treatment failure or suggestion of moving to next line of treatment. So, we try to continue sorafenib as long as possible. We created the new stopping rule as time to un-TACEable progression.
That way we can continue sorafenib 38 weeks. Then progression-free survival is significantly better in combination with TACE, in combination with sorafenib. And this is an ongoing trial. The PFS and OS are coprimary end points. There is a very important study method gate. Once PFS is met, then we look at the OS. So, we do not have to split the alpha. We are now waiting for the OS benefit. And this time, we showed the time to vascular invasion, time to extrahepatic spread, and time to disease progression, and we identified big difference. The hazard ratio is around 0.2. The TACE in combination with sorafenib prolonged time to stage progression, so we’re expecting the OS result.
Ghassan K. Abou-Alfa, MD: We’ll see how it goes, even though exactly as Dr. Kudo mentioned, sadly, so far, we have a lot of negative trials, among which, of course, is the SPACE study, and definitely it did not show benefit for the sorafenib combined with the TACE per se.
Transcript Edited for Clarity
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