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Emerging Approaches in Liver Cancer

Panelists: Richard S. Finn, MD, Geffen School of Medicine; Jordi Bruix, MD, Hospital Clinic University of Barcelona; Amit Singal, MD, MSCS, UT Southwestern Medical Center; Richard H. Marshall, MD, University Medical Center New Orleans; Arndt Vogel, MD, PhD, Hanover Medical School
Published: Wednesday, Aug 16, 2017



Transcript:

Richard S. Finn, MD: Speaking of some of the trials that were presented, unfortunately, we saw the negative results with tivantinib—a promising drug, but it did not meet its endpoint. Briefly, Jordi, can you give us your take on that?

Jordi Bruix, MD: Yes, c-MET is an important pathway in tumor progression dissemination. There was phase I, phase II randomized data, suggesting an efficacy of tivantinib blocking the c-MET pathway. The data were there. In biopsies, patients were enriched. The selection for these patients was c-MET positivity. It had all the steps of what is recommended to be done to select the target population. There’s also negative c-MET, but negative is negative and cannot be positive. So, it’s consistently negative.

Richard S. Finn, MD: Can we quote you on that? “If it’s negative, it’s negative, and it can’t be positive.” But one take-home message is, there was a lot of excitement about this because it was a biomarker-driven study. I think that’s still an important approach in liver cancer, and those studies are ongoing with other targets, like FGF19 and high AFP.

Jordi Bruix, MD: It supports what Amit said: that you take biopsies because you have research going on. You do ethical approval on all these things, and then it’s feasible. It’s feasible, doable, and it’s worth it to be done. But it’s research.

Amit Singal, MD, MSCS: Yes.

Richard S. Finn, MD: No discussion of cancer medicine, in 2017, is complete without talking about immuno-oncology. These drugs are rapidly changing the landscape across every discipline. And not unusually, drugs that are very exciting filter into liver cancer rather late. Can you comment, Amit, on where we are with the immuno-oncology agents?

Amit Singal, MD, MSCS: Yes. As you said, we’ve already seen these trials come out in other cancers, and we’ve seen very promising results and positive trials in other cancers. We have trials currently ongoing, and we’ve seen some interim results from the phase II data in terms of nivolumab in hepatocellular carcinoma. I think the phase II data—they’ve been presented, now, several times, including at the 2017 ASCO Annual Meeting—look promising. They’re very exciting. You see high objective response rates both in sorafenib-naive patients who refuse sorafenib, as well as in sorafenib-experienced patients, ranging anywhere from 10% to 20%.

However, I’ve learned, in my relatively short career, to take a little bit of cautious optimism. We’ve seen promising phase II data that we get very excited about, and then the phase III studies fall flat on their faces.

And the other thing that’s ongoing is the phase III data, in terms of frontline therapy. That trial is finished enrolling in most site
s.
Richard S. Finn, MD: And that study was an open-label study of nivolumab, the PD-1 inhibitor, versus sorafenib.

Amit Singal, MD, MSCS: Yes. That study has finished enrolling in most sites, although I think it’s still enrolling some in China at this time. My understanding is that we should hear results in 2019. Once again, I think the phase III data are going to be the final data in terms of really knowing if this provides a survival benefit. In the meantime, the phase II data looks promising, but I think that we should take a little bit of cautious optimism.

Richard S. Finn, MD: These initial findings were published by Drs. El-Khoueiry and Sangro in Lancet just the other week. And at the 2017 ASCO Annual Meeting, they presented a very provocative 26-month survival in the frontline setting. But I think many of us would agree, standards-of-care practices are made on phase III data. There are a lot of different immuno-oncology options and, now, combination immuno-oncology options.

Pembrolizumab is being studied in a phase III study for the second-line setting. And even now, the interest in taking some of our kinase inhibitors and looking at them in combination, it’s clearly a very exciting time in liver cancer research.

Before we end the discussion, I’d like to ask each of our panelists to provide some final takeaways regarding what we covered in the program today. We’ll start with you, Dr. Bruix.

Jordi Bruix, MD: The audience has to realize that liver cancer is not a disease with a dismal outcome. There are lots of things to be done. We need to keep doing research and not apply the wishful thinking. We will have lots of pressures to say, “We can do radioembolization” or “Nivolumab is optimistic.” If we do not maintain doing research in the field with proper trials, proper follow-up, and careful scrutiny, we are going to have a real mess, because patients will ask, or investigators will decide, to jump from one to the other. And at the very end, we will have no advancement. My recommendation would be to keep our research in place, discipline organizations, and get better results and wait for the phase III data. The rest is wishful thinking.

Richard S. Finn, MD: Dr. Marshall?

Richard H. Marshall, MD: I’d like to stress the importance of a multidisciplinary setting for these patients. They come in and, really, they have 2 separate diseases. They have an underlying liver disease and a cancer on top of that. It’s crucial to get these patients in, quickly, to multidisciplinary settings, so that we don’t wait to start treatments that could extend their life or quality of life. That, I think, is extremely important.

Richard S. Finn, MD: Dr. Singal?

Amit Singal, MD, MSCS: First, I’d like to reinforce what Jordi said, in terms of having discipline and really following the evidence base, and not just doing something because we can. But then, the second point is, really, that we have a lot of therapies that are coming out. We know that prognosis is really driven by early detection. The earlier you find the tumor, the better the therapies that you have. And so, screening your at-risk patients is really crucial. Then, also, as you transition to this, you’re going to see people transition from therapy to therapy in a timely fashion; not to continue doing locoregional therapy just because you can, but to transition to systemic therapy in a timely fashion, so you can use these now effective therapies.

Richard S. Finn, MD: Dr. Vogel?

Arndt Vogel, MD, PhD: I can only continue to emphasize what has been said before, and I think it’s really great that we now have a lot of clinical trials that we can discuss. We have something where we can build on our decisions, and I think it’s also important that we continue to have negative trials. Specifically, in these negative trials, such as the SARAH trial and SIRveNIB trial, there was a lot of visual thinking on what Y-90 can achieve in hepatocellular carcinoma. I think this puts this option in a more realistic perspective.

And on the other hand, we have positive trials, finally, for systemic therapies in the first-line and second-line settings. It’s getting more exciting and interesting to decide on the best treatment for our patients, and we have a lot of argument to switch from local therapies to systemic therapies.

Richard S. Finn, MD: It’s one really exciting time in liver cancer research. Thank you all. This discussion has been great. On behalf of our panel, we thank you for joining us for this Peer Exchange® discussion.

Transcript Edited for Clarity

Slider Left
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Transcript:

Richard S. Finn, MD: Speaking of some of the trials that were presented, unfortunately, we saw the negative results with tivantinib—a promising drug, but it did not meet its endpoint. Briefly, Jordi, can you give us your take on that?

Jordi Bruix, MD: Yes, c-MET is an important pathway in tumor progression dissemination. There was phase I, phase II randomized data, suggesting an efficacy of tivantinib blocking the c-MET pathway. The data were there. In biopsies, patients were enriched. The selection for these patients was c-MET positivity. It had all the steps of what is recommended to be done to select the target population. There’s also negative c-MET, but negative is negative and cannot be positive. So, it’s consistently negative.

Richard S. Finn, MD: Can we quote you on that? “If it’s negative, it’s negative, and it can’t be positive.” But one take-home message is, there was a lot of excitement about this because it was a biomarker-driven study. I think that’s still an important approach in liver cancer, and those studies are ongoing with other targets, like FGF19 and high AFP.

Jordi Bruix, MD: It supports what Amit said: that you take biopsies because you have research going on. You do ethical approval on all these things, and then it’s feasible. It’s feasible, doable, and it’s worth it to be done. But it’s research.

Amit Singal, MD, MSCS: Yes.

Richard S. Finn, MD: No discussion of cancer medicine, in 2017, is complete without talking about immuno-oncology. These drugs are rapidly changing the landscape across every discipline. And not unusually, drugs that are very exciting filter into liver cancer rather late. Can you comment, Amit, on where we are with the immuno-oncology agents?

Amit Singal, MD, MSCS: Yes. As you said, we’ve already seen these trials come out in other cancers, and we’ve seen very promising results and positive trials in other cancers. We have trials currently ongoing, and we’ve seen some interim results from the phase II data in terms of nivolumab in hepatocellular carcinoma. I think the phase II data—they’ve been presented, now, several times, including at the 2017 ASCO Annual Meeting—look promising. They’re very exciting. You see high objective response rates both in sorafenib-naive patients who refuse sorafenib, as well as in sorafenib-experienced patients, ranging anywhere from 10% to 20%.

However, I’ve learned, in my relatively short career, to take a little bit of cautious optimism. We’ve seen promising phase II data that we get very excited about, and then the phase III studies fall flat on their faces.

And the other thing that’s ongoing is the phase III data, in terms of frontline therapy. That trial is finished enrolling in most site
s.
Richard S. Finn, MD: And that study was an open-label study of nivolumab, the PD-1 inhibitor, versus sorafenib.

Amit Singal, MD, MSCS: Yes. That study has finished enrolling in most sites, although I think it’s still enrolling some in China at this time. My understanding is that we should hear results in 2019. Once again, I think the phase III data are going to be the final data in terms of really knowing if this provides a survival benefit. In the meantime, the phase II data looks promising, but I think that we should take a little bit of cautious optimism.

Richard S. Finn, MD: These initial findings were published by Drs. El-Khoueiry and Sangro in Lancet just the other week. And at the 2017 ASCO Annual Meeting, they presented a very provocative 26-month survival in the frontline setting. But I think many of us would agree, standards-of-care practices are made on phase III data. There are a lot of different immuno-oncology options and, now, combination immuno-oncology options.

Pembrolizumab is being studied in a phase III study for the second-line setting. And even now, the interest in taking some of our kinase inhibitors and looking at them in combination, it’s clearly a very exciting time in liver cancer research.

Before we end the discussion, I’d like to ask each of our panelists to provide some final takeaways regarding what we covered in the program today. We’ll start with you, Dr. Bruix.

Jordi Bruix, MD: The audience has to realize that liver cancer is not a disease with a dismal outcome. There are lots of things to be done. We need to keep doing research and not apply the wishful thinking. We will have lots of pressures to say, “We can do radioembolization” or “Nivolumab is optimistic.” If we do not maintain doing research in the field with proper trials, proper follow-up, and careful scrutiny, we are going to have a real mess, because patients will ask, or investigators will decide, to jump from one to the other. And at the very end, we will have no advancement. My recommendation would be to keep our research in place, discipline organizations, and get better results and wait for the phase III data. The rest is wishful thinking.

Richard S. Finn, MD: Dr. Marshall?

Richard H. Marshall, MD: I’d like to stress the importance of a multidisciplinary setting for these patients. They come in and, really, they have 2 separate diseases. They have an underlying liver disease and a cancer on top of that. It’s crucial to get these patients in, quickly, to multidisciplinary settings, so that we don’t wait to start treatments that could extend their life or quality of life. That, I think, is extremely important.

Richard S. Finn, MD: Dr. Singal?

Amit Singal, MD, MSCS: First, I’d like to reinforce what Jordi said, in terms of having discipline and really following the evidence base, and not just doing something because we can. But then, the second point is, really, that we have a lot of therapies that are coming out. We know that prognosis is really driven by early detection. The earlier you find the tumor, the better the therapies that you have. And so, screening your at-risk patients is really crucial. Then, also, as you transition to this, you’re going to see people transition from therapy to therapy in a timely fashion; not to continue doing locoregional therapy just because you can, but to transition to systemic therapy in a timely fashion, so you can use these now effective therapies.

Richard S. Finn, MD: Dr. Vogel?

Arndt Vogel, MD, PhD: I can only continue to emphasize what has been said before, and I think it’s really great that we now have a lot of clinical trials that we can discuss. We have something where we can build on our decisions, and I think it’s also important that we continue to have negative trials. Specifically, in these negative trials, such as the SARAH trial and SIRveNIB trial, there was a lot of visual thinking on what Y-90 can achieve in hepatocellular carcinoma. I think this puts this option in a more realistic perspective.

And on the other hand, we have positive trials, finally, for systemic therapies in the first-line and second-line settings. It’s getting more exciting and interesting to decide on the best treatment for our patients, and we have a lot of argument to switch from local therapies to systemic therapies.

Richard S. Finn, MD: It’s one really exciting time in liver cancer research. Thank you all. This discussion has been great. On behalf of our panel, we thank you for joining us for this Peer Exchange® discussion.

Transcript Edited for Clarity
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