Case 1: Treatment Response Rates & the Role of IR



Ghassan Abou-Alfa, MD, MBA:I’ll go back now to the case, and we spoke about lenvatinib. Is there anything you don’t like about lenvatinib? Adverse effects?

Farshid Dayyani, MD:That’s a very good question. There’s a distinct adverse-effect profile between sorafenib and the lenvatinib. If you look at the REFLECT trial, you will get more grade 3 hand-foot syndrome PPE [palmar-plantar erythrodysesthesia] in the sorafenib arm versus lenvatinib, which is more defined by generalized fatigue, weight loss, hypertension, and proteinuria, reflecting the more potent VEGF receptor inhibition. Clearly, it’s not a walk in the park. We have to be aware of the toxicities and actively manage them. There are some distinct features you have to pay attention to with lenvatinib.

Ghassan Abou-Alfa, MD, MBA:No, I totally agree. If anything, I think we all recognize it and are stressed by it. Especially the hand-foot syndrome with sorafenib can be really quite stressful, even though I give credit: some people really know how to master managing it. But nonetheless, the lenvatinib profile is rather more appeasing in regard to management because at the end of the day, the hypertension is easily controlled. At the same time, definitely a little maneuvering in regard to diet and appetite can help a little in regard to these symptoms. But also, last point, I was really very intrigued by the response rates you brought up. Let me ask you: what’s modified RECIST?

Farshid Dayyani, MD:Modified RECIST really looks at what makes sense, which means the viable part of the tumor. Instead of measuring the entire tumors—which might be a 90% narcotic—and show no change in size in the largest diameter, modified RECIST measures the largest diameter of the hypervascular part, or the part that is actually still viable. That becomes biologically much more relevant in the treatment of hepatocellular carcinoma.

If you look at the correct way, the modified RECIST way, then suddenly the response rate goes from mid-20%, about 24%, to 40% or 41%. That puts the activity of both agents much more into perspective.

Ghassan Abou-Alfa, MD, MBA:Riad, back to you 1 point. We proudly are able to talk to you guys now in IR [interventional radiology], and if nothing else, for us in oncology, now we can talk about response. We didn’t have response before. We’re very proud of that. To be fair, what does it mean to you? We tell you we have a lenvatinib response rate of 41% by modified RECIST. How do you read what we do?

Riad Salem, MD:Yes, Ghassan, you’re absolutely right. Historically, with interventional radiology with locoregional therapies, we have been the ones to enjoy the high response rates, no doubt about it. But now with the advent of some of the new therapies, clearly you’re catching up, and the response rates are very impressive. Now what does that mean?

I think response to a patient makes a lot of sense. It’s meaningful, it’s certainly something patients want to hear, they want to know what the tumor looks like: is it small or is it dead, etc? Can we cut it out? But frankly, it also extends the narrative to something that’s very new. Historically we used to talk about locoregional therapies for downstaging, but now theoretically, as we start to study this, can we start to think about downstaging with systemic agents?

These are the facts. This is what I’ve observed based on the literature. I think we’re going to have to be careful as to how we measure tumors with modified RECIST and whether those methods are validated and whether those methods are accepted. But there’s no doubt that now that narrative is part of the systemic agent, something that has been usually uniformly enjoyed by interventional radiology.

Ghassan Abou-Alfa, MD, MBA:I like that very much. If anything, we’ve learned quite a bit here. No. 1 is that early diagnosis and screening are very critical, as Dr Amit Singal mentioned. No. 2 is that understandably, if there’s a potential for a curative intent—surgery, RFA [radiofrequency ablation], or transplant—we are all for it.

Sadly, as we learned from this case—and we see it with many cases—recurrence is a possibility. If anything, there was a little bit of a debate about the second RFA. Nonetheless, to cross that bridge, we have seen that ultimately patients recurred and now have systemic disease. We spoke a lot about liver functionality and the importance of making sure that we keep patients, or make sure we manage patients the best as possible as a team, at Child-Pugh A score for chronic liver disease, with good liver function, relatively speaking.

Ultimately, when we need to use systemic therapy, thankfully, as Farshid mentioned, we have many choices, among which nowadays are sorafenib and lenvatinib. We heard quite a bit about lenvatinib—if anything, the new advantage, being an anti-FGFR, is that it really has added certain perspectives we have not seen before with sorafenib. Among which, for example, are response rates, which as we heard are 26% in regard to RECIST 1.1, up to 41% with modified RECIST. More important is that ultimately, the patients are living with an appropriate extension of life, as we have seen with the SHARP trial or with Asia-Pacific in regard to sorafenib. And now we’re seeing it with the REFLECT trial with lenvatinib.

Transcript edited for clarity.

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