番茄社区

In this exclusive roundtable video from 番茄社区, 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 , of Memorial Sloan Kettering Cancer Center in New York City, in this first of four episodes, in which they discuss the clinical impact of the and studies.

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.

And we'll start first with Dr. El-Khoueiry, and I'll start with the subject that really took a good piece of the presentations at the GI ASCO in San Francisco, which is biliary cancers. And we were all excited about the SWOG 1815 study that looked into gemcitabine, cisplatin, and nab-paclitaxel [Abraxane]. Tell us what happened.

El-Khoueiry: Yeah, so the SWOG 1815 study was the first randomized phase III trial for advanced biliary cancers in the U.S. to ever be completed actually. And to give credit, this was done under NCI [National Cancer Institute] sponsorship in the National Clinical Trials Network. So, across the cooperative groups, it was a very collaborative effort. It was based on phase II data that showed that gemcitabine, cisplatin, and nab-paclitaxel had resulted in a promising response rate and an intriguing median OS [overall survival] of 19 months.

So based on that, a phase III trial was planned, which was SWOG 1815 that randomized patients to the triplet versus the standard of gemcitabine and cisplatin. Of course, the study was designed prior to the TOPAZ data where the addition of durvalumab [Imfinzi] to gem-cis showed survival benefit.

It was a 2:1 randomization, and in a nutshell, this was a negative study. So there was no improvement in median overall survival between the triplet and the standard doublet. There were several stratifications and planned subgroup analyses. Of course some of these become quite small. But there did seem to be a signal in two subgroups where the triplet seemed to perform better in terms of response rate and survival, which are patients with locally advanced disease and gallbladder cancer.

So, as far as advanced disease is concerned, it's a negative study. The triplet will not move forward and not become the new standard of care, but it may be worthwhile exploring it in different settings for those subgroups of patients. Of course, that's hypothesis-generating at this point.

Abou-Alfa: I love very much what you said, and I especially would like to express to our colleagues that this is to be evaluated further. In other words, we don't go to clinic and we start using the same therapy for an adjuvant approach or even for a neoadjuvant approach, as you said, or even for gallbladder cancer. So we just have to wait for more data. Fair enough.

El-Khoueiry: Correct.

Abou-Alfa: Good. So now with this, you also yourself presented in regard to the IMbrave151. Tell us what IMbrave151 is first?

El-Khoueiry: So, you know, this is a study that was really designed to evaluate concurrent VEGF and PD-L1 inhibition in advanced biliary cancers. So it was a signal-seeking trial, hypothesis-generating study. So it doesn't have a lot of power. It was really looking to compare two experimental arms and decide which one to take forward.

And the randomization was between gemcitabine, cisplatin, atezolizumab [Tecentriq], bevacizumab [Avastin] versus gemcitabine, cisplatin, atezolizumab, and placebo. So it's a double-blind placebo-controlled study.

So in that study the primary endpoint was PFS [progression-free survival], and there was a slight numerical difference -- 8.3 versus 7.9 months -- with a hazard ratio of 0.76 or so. So maybe slightly favoring the bev arm, but not sufficiently to say this is a winner to take forward.

Now what's still cooking is that the median overall survival is not really mature, has not been reached for the experimental arm with bev and atezol, so longer follow-up is needed for that.

The 6-month PFS and the 6-month OS favor the bev arm as well. Response rate is similar across both arms and no new safety signals.

So, as it stands currently based on the PFS, there's no major improvement here. This will not move forward as it stands now, but with longer OS follow-up, we will see if we have another signal to look at. And of course, correlative studies are ongoing.

Abou-Alfa: That's great to hear. And again, one more time exactly as you wisely said, this is not necessarily something that we will jump on to be a standard of care.

Already, you mentioned the durvalumab plus gemcitabine-cisplatin, this is standard of care, of course, from a phase III clinical trial, and we're still bound by the phase III clinical trial because especially with so many advances in regard to therapies, we have to wait until we prove the survival component.

And I think a good example of that, exactly what you just mentioned, for example, with the SWOG 1815 study, where really the ... information will have to be measured by a phase III clinical trial that will look not only in outcome, but also in any potential adverse events and any other complication with therapy. That's great. Thank you so much for that.

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