Unresectable HCC with a History of Hepatitis C Virus - Episode 3
Ghassan K. Abou-Alfa, MD:As we noticed, the patient ends up on lenvatinib. At the moment there are at least, or actually there are only 2 drugs available at the moment as first-line therapy and both are FDA approved. Sorafenib, which we’re all very familiar with, it has been on the market for almost more than 11 years, and it was really the sole choice of therapy that’s available for all patients. But as of August 2018, we have the event of lenvatinib as an FDA-approved therapy, based on a noninferiority study where it was compared [with] sorafenib in this phase III trial, which was already published inThe Lancet.
The lenvatinib, and I would say that I’m happy that the patient was given lenvatinib because the drug really works. It’s very important here for all of us as oncologists, and also as a pathologist, is to understand that the noninferiority concept is not something that we’re very used to. If anything, we should not really read it as being, oh, they were equal; it’s not better so why bother. No, absolutely not. This is a very highly choreographed and very well-elucidated statistical design that will allow us to either prove or disprove the noninferiority, per se.
Now for all of us as oncologists, hepatologists, different disciplines, noninferiority concepts are a little bit difficult to understand. And it’s very important to really focus that at the end of the day it’s not about, oh, it wasn’t better, then maybe there’s no difference. It’s really was approved to reassure that they are equal. There are statistical nuances that are important that regard to develop that study or were required to develop that study.
The outcome were 13.6 months improvement in survival for the lenvatinib arm, versus 12.3 [months] for the sorafenib, and it was statistically significant, there was no difference of any kind or shape.
Now somebody might wonderlike wait a minute, we are used to sorafenib 10.7 months from the SHARP Trial, how come here we’re 12.3 [months] and lenvatinib [at] 13.6 [months]? Well we’re not very sure. But, however, the demographics of the patients will tell us there was no difference in regard to the population compared the prior studies. However, we all understand that our experience now with the tyrosine kinase inhibitors have continued to improve, and as such maybe better management, better earlier referrals, better multidisciplinary approach could have all have happened in regard to that improvement in outcome.
One argument that patients were probably mostly hepatitis C, I would say maybe but that’s not necessarily was 100% normal in regard to that study. But, again, I would say that the demographics have shown in any subgroup analyses that everybody did benefit from the drugs.
Another important piece about that study is that the progression-free survival almost tripled in the lenvatinib compared [with] the sorafenib. And fascinating along that line, the response rates were amazing. As we all know, the sorafenib response is really almost inexistent.
The RECIST 1.1 [Response Evaluation Criteria in Solid Tumors], which as we know is the 1 linear evaluation of the tumor, has shown in regard to the lenvatinib a response rate somewhere between 20[%], 25%, and modified RECIST showed the response rate more than 40%, so like 40[%] to 45%. And one wonders, like how come? And I have to say, the drug clearly does really work and it does really shrink tumors.
I had hands-on experience with it and I was really rather impressed with the outcome that it can provide. The modified RECIST, by the way, is very important to understand that because it is really rather than delineating everything like in 1 dimension like RECIST 1.1, actually it depends on another dimension, which is the actual necrosis that can occur within the tumor. Because tumors, we know, they can die within and you can see this on any good imaging, especially if 3 phase or 4 phase CT [computed tomography] scan of the liver or an MRI [magnetic resonance imaging], per se.
And one nice thing about the lenvatinib versus sorafenib data is that it showed this improvement in response…by modified RECIST, which was done in a prospective fashion. [I give] a lot of credit for the investigator on the really great effort. And it’s something that we need to remember that our radiologists need to be rather familiar, aware, and hopefully experienced in regard to how to evaluate the tumors by modified RECIST to ensure that we value that potential value outcome for the patients.
Transcript edited for clarity.
A 60-Year-Old Male With Unresectable HCC and a History of HCV