乌鸦传媒

In this exclusive roundtable video from 乌鸦传媒, three expert leaders in the field of gastrointestinal cancer discuss the latest emerging data presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.

Moderator , of Memorial Sloan Kettering Cancer Center in New York City, is joined by , of the University of Southern California Norris Comprehensive Cancer Center in Los Angeles, and , also of Memorial Sloan Kettering Cancer Center, in this third of four episodes, in which they discuss the interim data from the .

Following is a transcript of their remarks:

Abou-Alfa: Well, hello everybody, and great seeing you again. And whoa, we are still kind of wrapping up from GI ASCO, and it's still going on with a lot of information that we thought, why not have a roundtable and discuss some of the new things that were evolving. We learned from each other, a lot of things that we learned and a lot of things that we reflected on.

So, as you know, my name is Ghassan Abou-Alfa from Memorial Sloan Kettering Cancer Center in New York. And today I would like to welcome my two dear colleagues, Dr. Anthony El-Khoueiry from the University of Southern California Norris Cancer Center, and Dr. Steve Maron, dear colleague, also from Memorial Sloan Kettering Cancer Center in New York.

I saw, if I recall, at GI ASCO there was a study on tislelizumab in regard to gastric cancer. And if you don't recall, or you can tell me what you think, and this is from our good friend Markus Moehler from Germany. Do you remember that, anything about that?

Maron: Oh, yeah, the updated RATIONALE data. Yeah, we're gifted enough to have so many immunotherapy plus chemotherapy trials in esophageal gastric cancer right now that we really just have an incredible number of agents to use that are benefiting our patients. Tislelizumab is one of the newer ones on the block that really has shown dramatic progression for the overall survival benefit.

Abou-Alfa: Yeah, I hear you. We'll just have to wait for more. And by the way, I mean, I agree with you, congratulate all colleagues who really contributed markedly to all those studies. Among which, of course, our dear colleague Dr. [Yelena] Janjigian at Memorial, and Dr. Moehler as well. I'm always joking that I have to say this story between Marcus and I. We were at a meeting together in Copenhagen one day, and literally a glass of water next to him, it moved, or he moved it by error on my computer and here we go, my nice computer splashed with water altogether. And we went to the hotel, tried to put it in rice to make it like absorb and nothing happened. That was very painful, my friend, to fly all the way from Copenhagen back to New York without a computer. Try that. It's painful.

Maron: I can only imagine.

Abou-Alfa: We always laugh about it, but thankfully it is behind us and we're good. But anyway, back to you, Dr. El-Khoueiry. So, tislelizumab, interestingly however in HCC [hepatocellular carcinoma], we have got some data as well. So tell us about that.

El-Khoueiry: Yeah, so again, reminder, tislelizumab is another anti-PD-1 antibody. And tislelizumab had a where it was compared to sorafenib [Nexavar] as a noninferiority study. To put this in context, we all know that both nivolumab [Opdivo] and pembrolizumab [Keytruda] had deep durable responses in phase I/II studies in HCC. However, when we went to CheckMate 459, that compared nivolumab to sorafenib as a superiority study, it was negative. So nivolumab was not superior to sorafenib, at least statistically for overall survival.

So tislelizumab had a different study, which was a noninferiority trial, and it was a positive study. So tislelizumab was found to be noninferior to sorafenib, and the adverse event profile was definitely more favorable for tislelizumab compared to sorafenib. And that translated into improved quality of life, at ASCO GI this year. So at ESMO [European Society for Medical Oncology] we heard about the noninferiority results, and [at] ASCO GI we heard about the favorable quality of life with tislelizumab.

And to put this in context further, now I want to go back to your study, Ghassan, that you presented, which is the at last year's ASCO GI, because there is a common message there. In HIMALAYA, there were two comparisons, tremelimumab [Imjudo]/durvalumab [Imfinzi] in combination versus sorafenib, and another comparison which was durvalumab versus sorafenib, durvalumab being the anti-PD-L1 antibody. And one of the important messages here is that durvalumab in that study was noninferior to sorafenib. So now we have two agents, one targeting PD-L1, one targeting PD-1, both of which have been shown to be noninferior to sorafenib.

Of course, in first-line HCC we still use combination therapy as the standard, either atezolizumab [Tecentriq]/bevacizumab [Avastin] or tremelimumab/durvalumab based on HIMALAYA. But for the patients who are not combination candidates and don't want to get a TKI [tyrosine kinase inhibitor], I think now we have options with durvalumab and maybe tislelizumab if it gets approved.

Abou-Alfa: I like the way you brought it up, and my question to you is, do you have in mind, because, respectfully, patients really will entrust us on what we provide, and of course we depend on data generated from clinical trials. In your mind, who is the patient that you might give durvalumab as a single agent or tislelizumab as you just mentioned, and not durva/treme, for example, who would that be?

El-Khoueiry: Yes, it's a tough question, Ghassan, because it's not a defined population, right? And this is going to be really dependent on physician-patient discussion, risk-benefit ratio, review of side effect profile, and review of goals of therapy. But I'll tell you, in practical terms, I think a patient with low tumor burden, slowly moving disease where I'm not worried about inducing a response, and the patient does not have concern about having maybe a slightly higher risk of immune-mediated complications, let's say if we did treme/durva compared to durva alone, so I think using durva alone in a patient like this would be reasonable.

The other space that's important to consider is patients with compromised liver function. And this is really outside of the approval, the regulatory approval space. A lot of patients with HCC have compromised liver function and there is a group with Child-Pugh B cirrhosis who have reasonably preserved performance status, and they have Child-Pugh B because of a high bilirubin/low albumin, maybe ascites controlled with diuretics, they could still have treatment for their HCC.

We do not have good safety data for the combinations. Whereas with single-agent PD-1, PD-L1 and their favorable adverse event profile, those could be useful agents in that space. And as a reminder, there was some data with nivolumab within Child-Pugh B 7 and 8 patients in a phase II cohort that showed feasibility of that approach and activity. So I think we can extrapolate that to durvalumab reasonably safely, in my opinion.

Abou-Alfa: Thank you so much for that.

Watch episode one: Two Biliary Tract Cancer Trials Took Center Stage at ASCO GI

Watch episode two: The Role of Checkpoint Inhibitors in Gastric Cancer

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