Episode 66: Biliary Tract Cancer Masterclass with Professor John Bridgewater

Biliary Tract Cancers - Cholangiocarcinomas and Gallbladder cancers are often seen as rare and aggressive cancers.

🎙️We tackle Biliary Tract Cancers with the exceptional Professor John Bridgewater.

🎙️Few people are as knowledgable & linked to a cancer as Prof Bridgewater is to cholangiocarcinoma.

🎙️Prof Bridgewater has led practice changing studies in this area and is an internationally renowned expert.

🎙️This group of cancers is more common than you think!

🎙️If you don’t know your gallbladder cancer from your cholangiocarcinoma the check it out wherever you get your podcast!!

Find out more about these cancers at AMMF – The UK's only Cholangiocarcinoma Charity

Also - Check the Transcript!!

Transcript

 
 Hello and welcome to this episode of the Simply Oncology podcast. Mike, we are going into territory which is more your territory than mine and we're today. Our podcast is going to be about biliary tract cancers. Mike. Absolutely. John. Yes. Uncharted territory for you. And actually, for quite a lot of people, this is a rare cancer.
 And we are delighted to welcome the Shining Beacon for biliary tract cancers in the United Kingdom. Professor John Bridgewater from University College London. John, welcome and thank you so much for your time today.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   0:44
 Thanks very much for having me.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   0:46
 John, I think even I work in the pelvis. But even I have heard of your work. So do you want to just give the listeners just a slight flavour? We don't need, you know, the extensive but a slight flavour of your kind of interest in biliary tract cancers.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   1:02
 With, with, with pleasure. So biliary tract cancers, just to take a step back and introduce everybody to the, to the, to the anatomy as such are cancers that arise from the biliary tract. So that's the bile ducts as they run through the liver.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   1:04
 Yeah.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   1:21
 Down into the pancreas and then out into the small bowel and these are known as intrahepatic clangiocarcinomas. If they're inside the liver and extra hepatic if they're found outside the liver.
 We also include gallbladder cancers because, after all, they arise from biliary epithelium. And indeed there are some, although they're not entirely equitable biological features about these malignancies, so you will understand from what I've tried to say that the anatomy is.
 Quite desperate, and these cancers can often present in very different ways the intra hepatics more systemic symptoms, the extra hepatics more with obstructive jaundice, and buried and the gallbladder cancers present with symptoms of gallbladder disease.
 So quite often with they are mistaken for Cholecystitis and that leads to significant delays and diagnosis of many people. So, a disparate group of cancers with a disparate set of presenting features.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)  2:35
 And all confined within a very tight area of anatomical clockwork, a little pouch underneath the liver to the bowel. It's not a huge area, but there's a lot happening.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   2:47
 Play song.
 There's a lot happening, and you've just intimated to as to the other primary difficulty with these malignancies, which is that they are situated in a very small, densely populated and difficult to reach area of the body making.
 Instigation treatment with palliative procedures and surgery incredibly difficult. Hepatobiliary surgeons are species amongst themselves, known for their ferocity and bravery, and, you know, I applaud every one of them because this is incredibly difficult work that they do.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   3:18
 Mm-hmm.
 We know anatomically, obviously there's a difference, but I think it'd be great to get your insights into how our increased understanding of the molecular changes in Biliary Tract cancer sort of is that. Does that mean that actually although this we all call lump it to biliary tract cancer, are we increasingly going towards well, Mike, but John, what we do?
 That just for me because I'm a beginner in this. How it's a rare cancer. How many cases are we getting of biliary tract cancers a year? And I have a figure in my head. It might be historical, it might be wrong, but that the median survival of.
 Advanced biliary tract cancer tends to be less than a year now. Hopefully that's changing, and hopefully you're going to talk about that, but how? How common is this?
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   4:14
 Yes, so often it's known as a rare cancer, but this is actually commonly because of underreporting, and we all know that various sources of public data like his data can be can be found to.
 To be really quite wanting in terms of their accuracy, indeed we published we published saying demonstrating how really there is a significant underestimate of this of the incidence of this malignancy, there's been work done by the AMF, the standard, the.
 The charity, which does a great job raising the flag for this cancer to indicate that there are, at least in the region of 3000 cases a year in the UK, the there was some data during COVID that we managed to get off.
 Of the of the heads data. So, in the in one of the COVID years, I think it was 2021. We've managed to get the diagnosis of every single person going into hospital with the diagnosis that year and there were about 3000 patients with the.
 Diagnosis of cholangiocarcinoma going into the hospital everywhere, so we reckon it's somewhere between 3:00 to 6:00, three to 6000 new patients a year, depending on depending on the classification. And also, if you include the gallbladders.
 So it's it's something in that area probably should be considered an uncommon rather than a rare cancer. The other way of putting it is that they never thought that we could do any studies in biliary tract cancer because it's an uncommon cancer. You'll never see anybody and so on and so forth.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   6:05
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   6:09
 In fact, the two leading studies that we've done in the UK and more than two studies, part of the ABC series have all recruited well ahead of schedule. And so it really is not as rare as as rare as is often thought.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   6:29
 Absolutely. And so if we go back to that work, I steered you away from the actual question, the actual question, which is, you know, do we think that actually all these cancers are the same or we've got an increasing understanding that in fact they are different extra hepatic and intra hepatic gallbladder cancer.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   6:34
 Yeah.
 Yeah.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   6:47
 Different kettle and fish altogether.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   6:48
 So yes and no. The you start really with the seller of origin. So the seller of origin of some of these cancers is, is different, some of the intra hepatics clearly arise from hepatocytes.
 And the pathology and the aetiology comes from things that damage the liver and as such, intrahepatic aetiology is very similar to that of HCC. The aetiology of extra hepatic tumours and indeed gallbladder cancers is somewhat.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   7:16
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   7:23
 Different. That's more an inflammatory aetiology and then there's the, the whole story of chronic inflammation related to liver flux. That's what. That's what causes this cancer in in the Far East where there's endemic liver flux.
 So there's a there's a range of etiologies providing a range of different biologies for this for this cancer. So in some ways in in some ways they are all completely different. This is reflected in some of the genomics that we know about these cancers now. So in the intro.
 All have a demonstrate a number of fusions which are clearly driver alterations and these fusions are undoubtedly consequent on the.
 On selection, pressure from liver damage of some type we know this because of what these particular fusions do. What these genes do. For instance the FGFR 2 gene is clearly related in to, to, to liver to liver metabolism and.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   8:22
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   8:37
 And similarly, the IDH 1 gene is also said clearly limited. So there's some clear easy to follow alterations that link well with the aetiology, the aetiology of distal glandular carcinomas, distal and hylaclangocarcinomas.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   8:49
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   8:55
 Is more as I suggested earlier, related to inflammatory causes and so there you get more Ras mutations. You don't get really get any of these fusions and so we find that the anatomy of these cancers speaks to the genomic ultra.
 In actually quite a clearly interpretable way, and it makes it makes it makes it interesting. So for instance, it's, if we find, say, an IDH 1 mutation in what we think is a cholangiocarcinoma, we've probably got the diagnosis wrong.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   9:34
 Mm-hmm.
 And with these different classifications and genomics, does that mean there's different treatment patterns or treatment choices? Are the chemotherapies relatively the same? I'm thinking in my head of urothelial cancer where we call the ureter the non identical twin of the bladder, it's similar.
 But it's not the same as more FGFR mutations in the urine. So, but we still, but we still start with very similar chemotherapy kind of hubs and then very similar immunotherapy treatments thereafter is that the same in biliary tract cancers.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   10:00
 Yeah.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   10:15
 Yeah.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   10:15
 It is very similar, but probably through bad management rather than rather than common sense. So the first line treatment for advanced biliary tract cancer, which is most of what we do.
 Is chemotherapy and immunotherapy says platinum gemcitabine durvalumab is the is the standard of care first line therapy across the planet and then but in something between a third and a half of all cholangiocarcinoma and biliary check cancers you'll find and what we call.
 An actionable alteration, a fusion, an amplification or a mutation that permits targeted therapy and. And really there is no real reason why we shouldn't be bringing those therapies forward into first line because on the face of it.
 They work much better with far fewer side effects. The reason we don't is because of the testing and the testing has is sometimes difficult to do because of the lack of tissue.
 And because of the lack of application of the results, once you get it the we know from feed of information that there were something like 1200 patients.
 Who had a request for genomic testing in the UK last year? This equates pretty closely to the number of patients who received first line treatment with cisplatin, gemcitabine, and durvalumab. If you test for 1200 patients, you would expect, for instance, something in the.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   11:47
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   12:01
 The region of 150 patients to have an FGFR 2 fusion. But the actual number of patients who then are treated with an FGFR drug last year in fact was 29. So there are two big drop offs here in the numbers and this this.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   12:16
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   12:21
 Boy, this comes right back to what we said right at the beginning about knowledge and education these. So the first big drop off is between the numbers of patients we expect to have this cancer around somewhere between 3:00 to 6000.
 And then the number of patients who actually receive first line treatment 1200 or so, the second big drop off is the patients who we expect to receive some targeted therapy probably somewhere between 3:00 to 500 patients a year.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   12:41
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   12:54
 And in fact, it's only a fraction of that, probably less than 1/3 of that. So the reasons for those two drop offs are probably complex and deserve a lot more discussion and and talk than.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   13:06
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   13:12
 Then I won't. We probably have time for.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   13:15
 Were you about to say then a simple podcast can manage?
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   13:20
 Simple podcast will undoubtedly help. Will undoubtedly begin the, the OR or strengthen. Hopefully, the process of education that that that's currently going on.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   13:32
 Hmm.
 But I think you really highlight the point that actually that biliary tract cancers are complex, they're complex in their aetiologies, but they're actually complex in their diagnostic pathways. They're complex in their treatments. They're complex in their symptomatology, these patients.
 Who present are usually unwell, becoming rapidly unwell, and the general phenotype of biliary tract cancer is that of aggressive disease. Is that something you'd agree with and that may well be contributing significantly to those drop off rates?
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   14:11
 I think you're absolutely, I thought. Well, no, I think it's very I think I think what you have just described is a very common perception that that you know these patients are sick patients and there's not a lot you can do and what you can do is very limited this.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   14:12
 For discussion.
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   14:29
 Is actually not true for sure. You do get a number of elderly patients who are septic, and you probably can't do a great tool more and that undoubtedly contributes to.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   14:32
 Mm-hmm.
 Yeah.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   14:47
 At least some of the drop offs in in the expected treatment that that I mentioned before. There are however another cohort of these patients which are in my view extremely treatable, so for instance.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   15:02
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   15:04
 The the spike the the high end of the increasing incidence point, the spike in Intra hepatics is among young women, sort of somewhere between 30 and 50 years old.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   15:15
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   15:19
 Is is where the big increase is coming and this is almost certainly something to that we are doing to our livers. We are not entirely sure the incidence of actionable alterations in these in these young women is quite high. And if you happen to have 1A fusion.
 That's always. That's always a bit of a red Letter day clinic when we find one of these, because that automatically adds 2 years to the survival of one of these young women, which is not, is, is. I think you know.
 A good thing the and that really goes for the other actionable alterations as well. There's an increasing list of these things. Her too is a good example. The Raff is it a good example?
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   15:56
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   16:10
 And IDH one is a good example. So these are the these are really the commonly established alterations that are out there that we're treating in one form or other at the moment. There is a long list of other alterations that are coming up in study.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   16:30
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   16:30
 MDM two and of course K Ras. There they are. Perhaps in the more experimental phrase at the moment, but really there's a lot we can do for these patients. And I think the image of an untreatable elderly sick.
 Person should we should work at changing that over the next few years.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   16:57
 And with this, you know you've mentioned in the advanced setting how a sys gem followed by Durvalumab is an international standard, but with these targeted agents with this very high drop off rate that you're describing between first line therapy and second line therapy.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   17:02
 Hmm.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   17:15
 This is something that I think is such a crucial battleground. The first line in any advanced cancer for me is the key battleground. Presumably, these targeted drugs need to come into trials which are incorporated into that first line setting.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   17:24
 Hmm.
 Yep. So that's as I tried to say earlier, that's been tried, it's a difficult thing to do because it takes time to do the testing. So even now the best genomic hub turn around time is around two to three weeks potentially.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   17:41
 Yeah.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   17:53
 Potentially a bit longer and it I mean it will get quicker and there are lots of projects on the way to improve that turn around time, but currently it's it's stuck at around A2 to three weeks minimum. Most patients will not wait that long.
 To find out whether they have an actual alteration and consequently the default position of starting on first line all comers, chemotherapy and immunotherapy is an understandable default that clinicians resort to.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   18:30
 But I think that you've also will come on to this now because it's an important area in Billy Tract is the is the ABC 10 study that you're running and is obviously running nationally in the UK and I think that's trying to trying to bring those targetable mutations into that first line.
 Even more, as a maintenance treatment, I don't know if it would you like to tell us a bit more about ABC 10?
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   18:53
 With pleasure. So ABC 10, it's taken us a little while to get it, get it going by a number of years. Part of the reason is that we had to incorporate multiple pharma into the.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   19:01
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   19:09
 Into the contract, providing US drugs to treat these actual alterations and essentially the patients have started on first line therapy and then randomised at 12 weeks to either the actionable drug primarily.
 Two FTFR 2, idh one and B RAF, but including a few other subsets of those, including FTFR. 2 mutations, for instance, and her two mutations and potentially some of the B RAF fusions as well.
 So. So some of these, so the maintenance or the other way of putting it sequential therapy with targeted therapies is the primary reason for doing ABC 10. Actually it turns out other things have.
 Appear to be terribly important as well, so the single thing that we've learnt already is about the testing and the incorporating the genomic hubs in the testing, getting them on board is a hugely important.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   20:14
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   20:23
 Important part of this we've got a collaboration with Gardent who do a Garden 360 for all our patients and you know very simply doing 2 tests is better than one.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   20:40
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   20:40
 The I think I think if it does nothing else, it will hopefully educate the community about the value and the huge importance of the testing of the testing story. The treatment bit is almost the easy bit.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   20:57
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   20:57
 It's because we know this stuff is good and we know it works and the question is whether it is whereabouts we put it in the schedule of teaching in the in the schedule of treatment at 12 weeks or subsequently. I imagine that all of these things.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   21:14
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   21:16
 Will be more effective at 12 at 12 weeks, but that's what the trial is looking at.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   21:22
 I was. I was going to say I would commend you on all of that work you've done particularly trying to get all of those arms open and available to the patients and also commend you on is the trial design where you allow centres to provide the cisplatin gem site have been developed locally.
 Before randomization and then obviously the active trial centre will take over the the targetable treatments. But I mean that just opens doors for these patients to be able to start on treatment quickly, but then also then potentially access a really interesting trial and I think that that is a that is a an achievement to have done because that is very unusual.
 To be able to actually do. Presumably, it helps the cost of the trial but, but yeah, but absolutely. If you need to start treatment immediately, then get on and start the standard of care treatment and then engage with the trial once you're established. Yeah. Brilliant.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   22:15
 It was designed to be as acceptable as possible, as accessible and acceptable as possible, and in fact that's turned out to be the case, much so the accrual is is well ahead of schedule.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   22:21
 Mm-hmm.
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   22:35
 The accrual was going to be 800 patients between US and the French by July 2027. We're going to hit 800 by July 2026.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   22:49
 Fantastic. This is going to be yet another biliary tract cancer that delivers its trial numbers early in this not rare, but just slightly less common. Cancer. Yeah, fantastic.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   22:49
 So the.
 And.
 Well, it gives us the opportunity, I think that the biggest value there is that it will give us the opportunity of expanding the study in fact to 1200 patients which were in the process of doing and that will that will give security to the.
 To the primary outcome of the study as and but the I mean once again the other thing that I think is terribly important here is that it will establish a regimen of testing. It will establish a routine of testing because we will have 1200 patients worth of testing.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   23:31
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   23:38
 Data and we will be able to say really very clearly what to do, what works, what you should do, what you should not do and the amount of information the body of information that's going to provide will not. Nobody will be able to ignore that, no.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   23:39
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   23:58
 Investment body. No. No lab, no pathologist. They will not be able to ignore the, the, the, the sort of body of data that that's going to provide, yeah.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   24:10
 And that's part of the secondary gains that we get from every piece of research that we do. And as you say, really important to get the testing right. We've gone slightly back to front boom by the nature of this cancer because normally we talk about like the, the curative setting and then talk about the advanced setting.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   24:15
 Yep.
 That.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   24:30
 As you rightly pointed out earlier on, the more common scenario is the advanced setting, but there must be a kind of operative followed by adjuvant discussion that's happening in biliary tract cancers as well. Is there? Yeah, there is, there is good.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   24:47
 Actually, sure enough, there is the so that we've run a number of studies. We've run originally the BILCAP study which established Cape site being as a standard of care we.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   24:58
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   25:03
 Have subsequently run the ACTICA study, which compared cisplatin gemcitabine to Capecitabine and currently there are now. There's now a commercial study looking at looking at immunotherapy in the adjuvant setting. We're in the process of.
 Designing an adjuvant targeted therapy study, so really based on the success of ABC 10, we're going to we're looking at we're looking at, we're looking at really a very similar study in the adjuvant setting that's.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   25:24
 Mm-hmm. Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   25:38
 Going to be that's definitely going to be more challenging patients getting to surgery for this cancer are infrequent, probably in the region of one in 10 patients. So that's going to be a more difficult study to run, but that's being designed at the moment.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   25:48
 Mm-hmm. Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   25:55
 The.
 And so those. So that's the adjuvant story, the new adjuvant story really has yet to kick off, but I think has huge potential. Once again it all goes back to the testing the in the new adjuvant setting, your targeted therapy.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   26:06
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   26:18
 Your FTFR twos and your her twos have response rates somewhere between 2:00 to three times that of conventional chemotherapy up in the 60s, and 70 percents. And so consequently you would expect there to be a good rationale for.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   26:29
 Wow, that that's huge.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   26:37
 Running a neoadjuvant study in in. In that situation, the logistics are trickier. The logistics of getting your patient, getting your testing and starting your drug, or while the patient has a cancer that needs to be treated.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   26:45
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   26:57
 That's going to prove more difficult and until we get better at testing more, more knowledgeable about testing and quicker at testing, that is much that is going to be quite difficult to run. But the quite frankly the obvious study to do next.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   26:59
 Hmm.
 Yeah.
 And what is the adjuvant chemo then because you mentioned build cap with capsized bean and the comparator to sys gem, presumably that hasn't read out yet, has it or no?
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   27:27
 That is not read out. It was going to be. It was going to be a late breaking abstracted ESMO this year. But I've just learned it's not. So I'm going to have to hang on a bit longer, hang on a bit longer.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   27:36
 OK, well I was. I thought it was OK. Maybe ask her next year. Who knows? OK, and but I think we're not neoadjuvant is a slightly different setting, but we do see.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   27:40
 Yeah, yeah, yeah.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   27:51
 Good responses to these treatments, and I think this is about the changing that the changing narrative to this type of cancer because there is, there is a lot of negativity within the medical community relating to this I've seen with my patients. They go well, you know a surgeon will say well, there's nothing much we can do about this on your way but actually.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   27:57
 Absolutely.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   28:10
 I'm sure you've had experiences where you someone is upfront and resectable, but not obviously metastatic and they have fantastic responses and can have significant responses to cisplatin, gemcitabine, and durvalumab and then can potentially become resectable.
 So that there are there are things that can be done. That's the key thing here, isn't it?
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   28:29
 Yeah. No, no, I think I think I think the public, the, the sort of medical bit of medical information that that must go out is that even though the.
 His historical perception of this cancer is one of untreatable and poor out, untreatable and untreatable cancer with poor outcomes that is actually not the case. There are some patients for which we can do really a very great deal.
 Both with molecular studies with molecular treatment and other treatments, and we have to you know, we have to give full credit to our colleagues, gastroenterologists here in terms of the advances they've made with keeping people alive.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   29:16
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   29:21
 With improving biliary drainage and indeed our surgical colleagues who resect these cancers, which are located in some of the most difficult to find, difficult to access places in the body.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   29:25
 Mm-hmm.
 And do you think you mentioned about how the framework of ABC 10 kind of helps shape that testing and the narrative around that, do you think if there was a neoadjuvant study, it would then help shift that mindset of, OK, this person's unresectable, but let's think about neoadjuvant.
 Adjuvant and the testing framework that's been organised and then there's that mindset of can we make this person operable as opposed to, well, they're not for an operation. Let's forget about that. And it's only if you bring it back and then.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   30:14
 Yeah.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   30:16
 What I'm talking about really is that secondary benefit of doing a NEO entryment trial.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   30:18
 Yeah.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   30:28
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   30:28
 Because we've known for some time that some patients who were previously thought to be inoperable have become operable with targeted therapies, particularly the FTFR 2 drugs. So last line treatment gets to surgery. I have a very modest list of these.
 But in there were a couple of first line studies looking at first line, FGFR 2 that failed because they couldn't get the testing right. But actually we know that a number of patients in those studies did get to surgery.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   30:59
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   31:05
 So I hope that one of the one of the happy circumstances that ABC 10 will provide is a number of patients who then go on to who receive who received this drug probably at the earliest point possible.
 Who then are able to go on to surgery and that will be that, you know that from a from a patient point of view that that's huge. That's emotionally, absolutely monstrous for, for, for, for, for a patient and their family to have that.
 Prospect to have that potential cannot be underestimated.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   31:42
 Mm-hmm.
 John, this has been brilliant. What? What do you think is the next big thing? Do you think that new argument story is the next big thing or is no, you're not like to say ABC 10 because you're involved. You're not like to say my thing is the next big thing. However, I suspect you will be part of the next big thing. But where do you see blue track?
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   31:58
 Oh.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   32:06
 Who's moving? What? What's the next big thing for it?
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   32:10
 Thank you. I my personal view is that we need to we need to copy some of our colleagues in in more in dare I say it better funded cancer areas. So I am.
 Instantly envious of our colleagues in lung cancer who have immense resources and lots of both academic and commercial funding for both clinical studies.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   32:32
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   32:45
 And incredibly importantly, the translational bit that goes with it. So you know as we know the single most successful and academically lauded lung cancer.
 Trial the Tracer X study does exactly that it puts in parallel all the genomic all the biological information. You'd want to know about a particular cancer with detailed clinical trial history. And if you have that combination, really you're at a different level.
 And actually that's what we need to do next.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   33:26
 Fantastic. John, that was a whirlwind master class of biliary tract cancer from someone who is so passionate about it and is very much flying the flag for this. Can I ask one last question before we ask for three takeaway points? What is the charity for biliary tract cancers?
 AMMF. Hey, what does that stand for?
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   33:46
 Yes.
 It's in fact the Alan Mormont of Memorial Foundation. It not an easily rememberable a memorable title. MMF is, is probably much easier and it's run it's run out of Essex in fact.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   34:03
 Yeah.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   34:09
 And they are really a very good bunch of people, provide a lot of information, a lot of support patients find their way to the MMS website and they and find it incredibly helpful.
 So you know any patients out there looking for a bit of support, please, please get in touch with these people. It's an excellent organisation.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   34:37
 John 3 takeaway points. What are the what are the big messages you want to get out there?
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   34:43
 The big messages are really #1. If you see a patient with Blue Ray attack cancer, please do not think that this is an untreatable and desperate situation where there is no hope.
 Far from it for a lot of these patients, we can transform their lives and get them back to normal. The tools we have, the tools to do this, we just need to get sufficiently organised to make sure it happens for every patient.
 That's number one. Number two for biology is everything. We understand quite a lot about the biology of this cancer. We have a lot more to understand about the biology of this cancer. It's completely revolutionised our treatment options.
 And can make huge differences to the lives of these patients. Some of these targeted therapies really have no toxicities and the number of patients I've had.
 On treatment who go back to work, you know is a is A, is a testament to that. So that's the. So the biology, the biology is the future and matching up your biology with your clinical trial is A is A is a.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   35:54
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   36:10
 Tried, tested, expensive but absolutely critical strategy and I guess the final take home as you'd probably expect me to say is always look for those trials, they're out there, they these patients are incredibly keen to participate.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   36:15
 Mm-hmm.
 Mm-hmm.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   36:30
 And, dare I say it, you know, we've had a reasonable run of good luck with these studies, particularly in the UK, particularly in the UK. We have managed to define the standard of care pretty much for the rest of the world some time.
 And really everybody should feel very good about that.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   36:53
 Thank you, John. That is that well, that's an amazing 3 takeaway points. Yeah, OK, that, that that nails it. Yeah. John, thank you so much for your time. Really great to have you on the show.
BRIDGEWATER, John (UNIVERSITY COLLEGE LONDON HOSPITALS NHS FOUNDATION TRUST)   37:04
 Pleasure.