Sorafenib and Lenvatinib Adverse Events

Transcript:Ghassan K. Abou-Alfa, MD: We’ll bring another drug to the table—lenvatinib. Tell us a little bit about your perspective, especially since you are a hepatologist. Of course adverse events [AEs] are critical for liver performance, and, of course, for patients as well. Did you see any difference in regard to the adverse events that really tells you that this is the same, better, or worse than sorafenib?

Amit Singal, MD: Yeah. So I think that the devil is always in the details in terms of the AE profile. So overall I think when you take a look at the proportion of people who had an AE, it’s pretty similar between the 2 drugs. But the devil is in the details in terms of which AEs you have. So, when you take a look at sorafenib, those patients have much higher proportions of hand-foot skin reaction. Then when you take a look at lenvatinib, they have higher proportions of patients who have hypertension, anorexia, fatigue, and then you can also get some nephropathy. So you can get some proteinuria with the lenvatinib. And so I think these things, when you take a look at the specific AE profile, there are notable differences, and at least from a hepatology perspective, these are very important when we talk to our patients, and that’s actually one of the things that we use in terms of trying to decide between those 2 drugs when we talk to our patients.

Ghassan K. Abou-Alfa, MD: Fair enough. So, Farshid, is lenvatinib FDA approved now? I know it is, but I would like to hear are you using it?

Farshid Dayyani, MD: I tend to believe that controlling cancer leads to better outcomes. And if a drug gives you higher response rates, I think if you select the patient correctly based on the eligibility criteria of the REFLECT trial, less than 50% involvement, not involvement of the major portal vein, I think that’s 1 of the misconceptions. Bringing it to the appropriate patient earlier, meaning the patient has better liver function and better underlying disease, you might have a benefit of controlling the disease longer in first-line treatment. So, based on that paradigm, I’ve certainly started using lenvatinib in first-line in the appropriate patients. You discuss, as Amit said, the adverse effect profile, and fatigue is certainly something to work with. You have to closely watch the liver function, you have to check the LFTs [liver function tests] very frequently initially. But I think if there’s 1 thing sorafenib taught us over the past 10 years is commit to the treatment and try to work around if you start with it.

Ghassan K. Abou-Alfa, MD: Along that line, let me make it simple. Are you happy with lenvatinib or are your patients happy with lenvatinib?

Farshid Dayyani, MD: It’s too early to tell and the majority of our patients go usually on clinical trials in the first line. So the experience is limited, but we have seen some responses in patients where I wouldn’t have expected those. We’ll see if that translates into the outcomes that we see in the REFLECT trial. Time will tell.

Ghassan K. Abou-Alfa, MD: Fair enough. Good. Katie?

Katie Kelley, MD: Yes, I think it’s an active drug and I have started to use it. As Amit alluded to, sometimes the AE profile is the guiding factor in which the drug to choose first-line in terms of how well hypertension is controlled, in somebody who may not have, despite our best efforts, perfect blood pressure control—I think sorafenib may be the preferable choice. Simply playing the numbers game that the rates of grade 3 and higher hypertension were lower. That said, generally our standard practice is to get blood pressure under control before starting either of these drugs or any of the TKIs [tyrosine kinase inhibitors] because that’s a critical factor in safety. And so the other factor, the rates of hand-foot syndrome are dramatically lower and that’s been my experience in practice as well, which is very meaningful for patients who do or don’t get that particular AE.

Ghassan K. Abou-Alfa, MD: Well, I’m happy to hear that if anything, most importantly it’s definitely, as we all agree, 2 choices is better than 1. On the other hand, I think, as Amit smartly said, sorafenib definitely brought in an answer and a choice of therapy, but at the same time it no doubt raised a lot of questions that of course were a trigger for more research that’s ongoing. The lenvatinib is really quite intriguing, and I like very much what Farshid kind of liked and started with by explaining the targets of the therapy. And no doubt there was a lot of efforts that was done before. They got to the FGF [fibroblast growth factor] family and the targeting of the FGF family which we know lenvatinib is pretty strong in regard to.

But it’s quite intriguing that the response rates were extremely high, and I have to admit that humbly being the first person who did the phase II study on sorafenib, I would say the response rates on the lenvatinib are robust, according to the RECIST 1.1 criteria, which show more than a 25% response rate. And by the modified RECIST, exactly as Katie was describing, which will look into the tumor from a third dimension, showing how alive or not alive it is, is 40.1%. That’s really incredible. On top of that, I hear that yes, we have to be recognizant in regard to the adverse events of the different drugs. And yes, we do recognize that all of them have side effects. But, again, as we’ve kind of alluded to from our friends is that maybe the hand-foot syndrome remains rather a difficult thing to tackle from the patient perspective because we’re touching our hands here.

We spend a lot of time and energy in regards to understanding better what the hand-foot syndrome is. Actually, I give lot of credit to our colleagues at Memorial Sloan Kettering Cancer Center, who were able to define ways to manage the hand-foot syndrome. And I totally agree with Katie, that the earlier we handle it, the better it is. Same as any other adverse events. On the other hand, the hypertension, yes, is manageable, and can definitely can be taken care of easily. And I like what Katie suggested, which is just to make sure that it’s controlled right from the start rather than later on in the game.

Transcript Edited for Clarity