Two Biliary Tract Cancer Trials Took Center Stage at ASCO GI

Two Biliary Tract Cancer Trials Took Center Stage at ASCO GI

In this exclusive roundtable video by MedPage todaythree leading experts in the field of gastrointestinal cancer Discuss the latest data presented on the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium..

moderation Ghassan K. Abou-Alfa, MD, of Memorial Sloan Kettering Cancer Center in New York City, is supported by Anthony B. El-Khoueiry, MD, of the Norris Comprehensive Cancer Center at the University of Southern California, Los Angelesand Steven Maron, MD, MSc, of the Memorial Sloan Kettering Cancer Center in New York City, in this first of four Episodes in which they discuss the clinical implications of the SWOG 1815 and IMbrave151 studies.

A transcript of their comments follows:

Abou Alfa: Well hello everyone and nice to see you again. And whoa we’re still in the process of wrapping up GI ASCO and it’s still going on with lots of information we thought why not do a roundtable and discuss some of the new things that have been developing. We’ve learned from each other, lots of things we’ve learned and lots of things we’ve thought about.

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

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

El Khoueiry: So yes, the SWOG 1815 trial was the first randomized phase III trial in advanced biliary cancer in the US that was ever actually completed. And to give credit, this was done under NCI [National Cancer Institute] Sponsorship in the National Clinical Trials Network. So it was a very collaborative effort between the cooperative groups. It was based on Phase II data showing that gemcitabine, cisplatin and nab-paclitaxel had resulted in a promising response rate and an intriguing mean OS [overall survival] of 19 months.

On this basis, a phase III study was planned, which was SWOG 1815, which randomized patients to the triplet versus standard of gemcitabine and cisplatin. Of course, the study was designed before the TOPAZ data, which added durvalumab [Imfinzi] compared to gem-cis showed a survival advantage.

It was a 2:1 randomization, and in short, this was a negative study. So there was no improvement in median overall survival between the triplet and the standard doublet. There were multiple stratifications and planned subgroup analyses. Of course, some of these get pretty small. But there seemed to be a signal in two subgroups where the triplet seemed to do better in terms of response rate and survival, namely patients with locally advanced disease and gallbladder cancer.

So in terms of advanced disease, it’s a negative study. The triplet will not evolve and become the new standard of care, but it may be worth investigating in different settings for these subsets of patients. Of course, this is hypothetical at this point.

Abou Alfa: I very much like what you have said and I would particularly like to say to our colleagues that this needs to be further evaluated. In other words, we don’t go to the clinic and start using the same therapy for an adjuvant approach, or even a neoadjuvant approach, as you said, or even for gallbladder cancer. So we just have to wait for more data. Because of me.

El Khoueiry: Correct.

Abou Alfa: Good. You have now introduced yourself to the IMbrave151. First, tell us what IMbrave151 is?

El Khoueiry: So, you know, this is a study that was actually designed to evaluate simultaneous VEGF and PD-L1 inhibition in advanced biliary cancer. So it was a signal-seeking study, a hypothesis-generating study. So it doesn’t have much power. It was really about comparing two trial arms and deciding which should go ahead.

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

Thus, in this study, the primary endpoint was PFS [progression-free survival], and there was a small numerical difference – 8.3 versus 7.9 months – with a hazard ratio of about 0.76. Perhaps the Bev arm is slightly favored, but not enough to say this is a winner to push forward.

What’s still boiling now is that median overall survival isn’t really mature yet for the experimental arm with Bev and Atezol, so it needs longer follow-up.

The 6-month PFS and 6-month OS also favor the Bev arm. The rate of response is similar in both arms and there are no new safety signals.

As it currently stands based on the PFS, there is no significant improvement here. This won’t move forward as it is, but with a longer follow-up of the OS we’ll see if we have another signal to watch out for. And, of course, studies are under way.

Abou Alfa: That’s good to hear. And again, again, just like you wisely said, this isn’t necessarily something we’re going to jump on as a standard of care.

You already mentioned durvalumab plus gemcitabine-cisplatin, which of course is standard treatment from a phase III clinical trial, and we’re still tied to the phase III clinical trial because just with so many advances in terms of therapies, we have to wait until we prove the survival component.

And I think a good example of that, exactly what you just mentioned, is for example the SWOG 1815 trial where really the… information needs to be measured by a phase III clinical trial that’s not just on the result will look, but also at possible adverse events and other complications of therapy. That’s great. Thanks a lot for this.

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