The Oncology Podcast

S3E9 The Oncology Journal Club Podcast: ESMO 2025 Special Part 2

• The Oncology Network presents The Oncology Journal Club Podcast • Season 3 • Episode 9

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Welcome to The Oncology Journal Club Podcast Series 3
Hosted by Professor Craig Underhill, Dr Kate Clarke & Professor Christopher Jackson | Proudly produced by The Oncology Network

Kate Clarke takes over hosting duties!

Join our expert trio — Professor Craig Underhill, Dr Kate Clarke and Professor Christopher Jackson — for the usual OJC antics in Part 2 of our ESMO Special.

Craig talks us through the GU and lung highlights, while the team each share their top ‘practice-changing’ abstracts. Plus, CJ chats with Susie Stanway about the upcoming London Global Cancer Week.

Expect nuanced analysis, sharp insights and the occasional cheeky joke along the way.

To learn more about The Oncology Network, subscribe to our free weekly Newsletter and listen to other fantastic podcasts, visit our website: www.oncologynetwork.com.au. You'll also find the Show Notes on the website with links to the abstracts, bios of our hosts and a downloadable Bingo Card😂

SPEAKER_02:

Welcome back to the Oncology Journal Club Podcast, brought to you by the Oncology Network. Today's episode is part two of our ESMO 2025 special. And yes, expect more bingo antics. I'm your producer, Rachel Bavin, and I'm once again joined by our Journal Club Dream Team, Professor Craig Underhill, Dr. Kate Clark, and Professor Christopher Jackson. Craig talks us through the key updates in GU and lung cancers. We also have a sneak preview of the upcoming London Global Cancer Week with Susie Stanway. For more information about the Oncology Network, including links to the abstracts discussed, head over to Oncolynetwork.com.au. Thanks for tuning in. Let's get started.

SPEAKER_04:

G'day, gada, g'day. Welcome to Istmo Part 2, 2025. Professor Underhill, how are you?

SPEAKER_00:

Good thanks, Dr. Kate Clark. How are you going? I'm scared about this today because normally I'm the one who's in control. But I'm going to be doing a bit of chatting about some of the lung and GU abstracts from ESMO.

SPEAKER_04:

So you know us, we'll be kind. Think of it like a job for a PhD defense.

SPEAKER_00:

You'll be kind to me.

SPEAKER_04:

Professor Jackson, okay, my ally. How are you down at Dunners?

SPEAKER_01:

Uh Calder. We've had a bit of a uh a weather fest these last couple of days. It's been snow, there's been hail, there's been unseasonal rains. It's almost like the climate's changing. No. Seriously? It's crazy. Anyway, Craig, I'm looking forward to uh Ezmo part two today and uh all of the Bratwurst jokes and uh pelvic radiotherapy analogies that you're going to be coming up with. So can you meet the standards set by the Mercurial Dr. Clark?

SPEAKER_04:

Where do you want to start, Greg? From the sublime to the ridiculous.

SPEAKER_00:

Oh, I was just gonna say I was hope everyone enjoyed part one. And so, yeah, part two will focus on some G U and Lung. I'll probably start with the G U. Chris stole my thunder in part one. I was gonna refer to the IMVigor 001 trial, late breaking abstract eight, looking at the role of CT DNA positivity and looking like that's predictive for using hegemon immunotherapy in muscle invasive bladder cancer. So I think that was one of the highlights of GU. So if people are interested in that, it is worth listening to part one. There was a couple of other studies in urethelial cancer. One was a phase two in HER2 expressing urethelial cancer, late breaking abstract O7. This was another new molecule for us to get our tongues around. Disatamab verdotin plus immunotherapy, which led to almost doubling of overall survival in advance HER2 urethelial cancer. So this was a phase three study comparing this new antibody drug conjugate, disatamab verdotin, to GEM and either cisplatin or carboplatin. The HER2 positivity rate in urethelial cancer varies in various reports, anywhere between 10 and 60%, but it's thought to be probably mostly at that upper range. So these included patients that had HER2, one or two or three plus standard IHC. The progression-free survival was 13 months versus six months with hazard ratio 0.36. Uh and the uh overall survival was 31 months versus 16 months with hazard ratio 0.5. So pretty impressive results. The patients with in receiving the disatamine uh verdotin plus toralipomab experienced uh less grade 3 treatment-related adverse events than the patients who received standard cisplatin or carbo and gem cytobine chemotherapy. There was 4% peripheral neuropathy rate, more adverse events with raised hepatic uh function tests and hematological toxicity. So the authors concluded that this uh toxicity was manageable.

SPEAKER_04:

Look, yeah. Yeah. Couple couple of questions from me, Craig. The anti-HER2 agents in this population, have they been tested before rather than the monochronous antibody drug conjugates? But Trastozimav and and Friends. Has that work been done?

SPEAKER_00:

I'm not sure. That's a really great question, uh Dr. Clark, but I don't know that answer. I presume there has been studies in this population with other HER2 agents, but this was a study done in uh Chinese population, the drugs being developed by a Chinese company. And so that was one of the first criticisms that it's a China alone uh population. And the other criticism of this study was the reference arms, probably no longer the standard of care in countries that now have Mfortomab and Pembrozen Mab available on the basis of ESMO last year. So it's a rapidly evolving field. And when this study was designed, the chemotherapy was the standard of care, but it's now actually been replaced. Although not every market has access to the M4Mab. But it's it's now meant that there's a it's quite a complicated field going forward because both HER2 and Nectin-4 um are enriched in these cancers and often overlap. So patients are HER2 positive are often nectin-4 positive. So there'll need to be ongoing trials to try and tease out what the new standard of care might be. But certainly interesting results, and you know, the conclusion from the uh discussant was that this study will obviously need to be broadened out into a more diverse population other than outs just uh in China.

SPEAKER_01:

Yeah, I think we have to really be super careful about uh comments like that, I think, because you know, we we often don't say this is only done in an American population. And you know, so I think discussants who say things like that have to be a little bit careful about sure, generalizability is an important feature of all randomized controlled trials. You do want to have your heterogeneous population, so it is extrapolatable to population study. Uh, but you wouldn't make that kind of comment if it was a Europe-only study or an American-only study, right? Um so you have to be a little bit careful about that. Second of all, I think that you know, China is clearly a very strong emerging player in drug development internationally. And I think that, you know, China had almost as many INDs as uh FDA uh did, and you know, Torapelamab is what a Chinese petty one, isn't it? So it's aiming for that fast follower status in neuroetherial uh cancer here also. I think we're gonna see an awful lot more renoussaceries coming out of mainland China in the near future.

SPEAKER_04:

And I think we should think about it as an opportunity. Yeah. I'm disappointed when people say this offers nothing novel. I'm like, well, it's 20% of the price. That's novel. Yeah. So let's start from there.

SPEAKER_00:

I'm gonna refer to a few other products coming out of China in this uh episode. So maybe maybe we need some to add something to our bingo card as uh this study needs to be redone in populations outside of China because this will come through a few times uh on this podcast. So, and I'm not saying that that's what I would say, I'm just saying that's what the criticism of this study is.

SPEAKER_04:

Because a less generous person would say, think of the wealthy white population, you know, how how are they going to respond to these drugs? Yeah, yeah. Right.

SPEAKER_01:

Yeah, and and I think we can anticipate and expect that you do have differences in pharmacodynamics and pharmacokinetics between populations. I mean, that's well established. We saw that with uh S1 and GI cancer. You know, we see that with capsidamine in uh different populations, we saw that with EGFR inhibitors and lung cancers uh also. I don't think we've got the same level of evidence to suggest that's true in uh the immune therapy era, but perhaps that's an area of active research to be considered.

SPEAKER_04:

Well, I think, Chris, as we are beginning to understand that it's a whole of person model for how immunotherapy reacts, and so it is modifiable that it's maybe it's not as clear as genetics, but environment. So I think that that's that's very interesting. Microbiome, right? Yep. All about the microbiome. Yeah. Craig, what else have you got for us?

SPEAKER_00:

So another bladder cancer study. So just mentioned before infortomab pembrozimab, which has now become, you know, one of the standards of care if you can get access to it in uh cisplatin ineligible patients. So this was a keynote 905 EV303 or lake breaking abstract two, which is perioperative infortomab fordotin plus pembluzimab, prolonging survival in muscle invasive bladder cancer. So this perioperative approach, we're seeing that time and time again in many cancers now. It seems to perioperative immunotherapy may be the way to go rather than just adjuvant immunotherapy. So this was a study done in giving some pre-operative doses of uh enfortima, verdotin, and Pembro uh before and after surgery in muscle invasive bladder cancer, and had quite um impressive results. So the headline results showed in terms of event free survival, it's not reached in the investigated arm and in the control arm 15 months hazard ratio's 0.4. So we obviously need longer follow-up to see the full survival advantage, but this looks to be very encouraging. Now, there was a again a difference in in some of the toxicity, and so there's some specific adverse events of of note with this combination of the dotin and pembrolizumab in particular. Um, there's some skin reactions, proofonuropathy, ocular disorders, and hypoglycemia.

SPEAKER_01:

Yeah, Craig, look, that's that is really impressive. I mean, a hazard ratio 0.4 in the perioperative setting is pretty strong in any cancer, isn't it? So that's clearly a a a big step forward for this cancer. And is this going to create a new bing standard of care in this tumour?

SPEAKER_00:

Well, perhaps it will, Chris. And just the perioperative approach, as I said at the start of the discussion of the abstract, is you know, this sort of interesting approach we're seeing with lung cancer, with gastric cancer, esophageal cancer. Um that this perioperative approach may be important to uh with an intact immune system, uh intact, you know, locoregional lymph nodes, you may get a immediate benefit and reduction in the tumour and an ongoing immune response during that break while people have surgery. We know surgery is immunosuppressive. People have to recover from it before they can have the treatment.

SPEAKER_01:

Yeah, I mean, are you seeing many other trials of perioperative management in uh in bladder cancer Craig? It's been a while since I treated it. Would it seem to be mostly preoperative or uh adjuvant in days gone by?

SPEAKER_00:

No, I think the that's right. Normally there's neoadjuvant approaches or there's adjuvant approaches, but this perioperative approach I think is quite novel, but as I said, fits in with really on what's going on in other other tumours.

SPEAKER_01:

I mean, certainly it's been very successful in melanoma, hasn't it, where you've got the exposure to the neoantigens at the time of exposure to IO being the giving the immune system chance to recognise those antigens and then wander in a muffin go.

SPEAKER_04:

Hungry enzymes. Yes. Hungry enzymes. Hungry enzymes. Um showing my age it's had. Interesting, Craig. I look, I still struggle with perioperative without an adaptive step, because it just doesn't make any sense to me. If you can see what you've done, then surely you should change your behaviour as a result.

SPEAKER_00:

That approach has been validated in melanoma, but I think that's still, you know, there's a whole field ripe for the picking there, isn't it? With trying that approach in uh clinical trials in other tumors.

SPEAKER_04:

Yeah, no, I I think you're right. I think it it needs melanoma were brave and made the appropriate plan for the trial. And and I think that's what we need to be thinking about when we're designing these trials, rather than just chugging on and giving 12 months of the agent because that's what we do. Is that all of G U?

SPEAKER_00:

All right, well, we've got a prostate cancer study. So this is looking at the role of enzymide plus ADT uh in biochemically recurrent prostate cancer, late breaking abstract 87. This is the embark study headline results, overall survival benefit with hazard ratio of 0.59. So this is a big difference. So these are patients who've PSA started to go up, but no radiographic evidence of metastases on conventional imaging after prostatectomy, radiotherapy, or both, with a doubling time of their PSA of less than nine months. So this is a now becoming an increasingly rare group of patients that have PSA going up, no evidence of recurrence because many patients nowadays uh have access to a PET scan. And we know that in that population, PET scan uh detects uh metastases in about 80% of the time. So at the time this study was designed, there wasn't such ready access to PSMA pets. Um, but we know now that you know about 80% of the time PET will detect metastases in this group. Nevertheless, this study showed a very impressive, was described the survival rate at eight years. The survival rate's 78.9% for the patients receiving ensolutomide plus ADT compared to 69% for ADT alone. And then they looked at some secondary endpoints, time to first use of a new antineoplastic therapy, statistically significant, clinically significant benefit from adding enzyutamide to ADT, hazard ratio 0.37, time to first symptomatic skeletal event uh 0.39 hazard ratio, progression-free survival on first subsequent therapy also showed clinical benefit with a hazard ratio 0.56. So, really showing that for patients who don't have detectable metastases with the rising PSA less than nine months, this is certainly a valid approach.

SPEAKER_04:

Craig, can we go over things slowly again? Yeah. So this trial, patients weren't PMSA staged.

SPEAKER_00:

Correct. Because that wasn't the standard when that was designed.

SPEAKER_04:

At the time, do you think that in the day of PMSA PET scans that this outcome is still that those patients who have not got PMSA pet positive disease but do have an elevated PSA will benefit from ensalutamide, etc.? Or do you think that they are a different group of people? Or or do you want to hazard the guess?

SPEAKER_00:

Yeah, well I don't know that the trial could ever be repeated and have the eight-year follow-up. I mean that's a problem, Kate. So yeah, it's an interesting question. But I think now we screen people out using the PET scans, and so we can then give them whatever's appropriate therapy based on whether they have locoregional recurrence, and if they haven't had radiotherapy, they might have that. Or if they've got metastatic disease, then they might be started on on ADT plus either an oral agent or may even receive chemotherapy uh six rounds at that time to maximize their response. So it's a going to be a rare population. So men with rising PSA, truly negative metastatic disease on pet, I think this probably does, given those results, it would be hard not to discuss that with the patient. So if you put them on ADT, they have many side effects, including um loss of sexual function. There was an arm in this study with just the enzyutamide alone without the ADT, didn't do as well, but they still did better than nothing. And so in the discussion, they talked about well, maybe that for some men, the single agent is actually a valid approach as well. But there was an A Australian New Zealand urological group study, ends up 1303, the ENSA rad trial, which was negative. So that was adding enzymutamide to radiotherapy in high-risk localized, locally advanced prostate cancer. So they didn't give to the ADT, but it was just a single agent drug, and it was a negative study that was presented the meeting as well. So individualizing care and discussion and MDT.

SPEAKER_04:

That's a lot, isn't it? It's like you know, there's so many. I haven't treated prostate cancer for a long time, and it just seems like it's getting more and more complicated and niche. And the radiation oncologists tell me they can retreat things they've treated before to some unbelievable high dose of case, they could do it again. Yeah.

unknown:

Yeah.

SPEAKER_00:

Yeah. And uh I think that's getting harder and harder to be able to do.

SPEAKER_01:

Stay up with that. What was the median overall survival in the ensoleudomide study, Craig?

SPEAKER_00:

Because the overall survival at eight years, so it wasn't median overall survival wasn't presented. They presented the overall survival at eight years, it was 78.9 versus 69.5.

SPEAKER_01:

Yeah, wow. So, I mean, you're talking about years and years and years on these drug treatment, Craig. So, you know, that's a huge burden of follow-up that has to be managed. But also it brings into stark focus those chronic low-grade toxicities as well. You know, some people say that a month of grade one toxicity is worse than a single day of grade three toxicity. So, you know, almost that toxic the year under the curve thing. Do they have any patient-reported outcomes there?

SPEAKER_00:

Oh, they will have collected that, but I didn't see that.

SPEAKER_01:

Not reported yet at this stage. Yeah. Because when you're talking about that lecture follow-up, you know, it starts to be the question, what what's it like in terms of uh patient experience really, which is often not well captured by that grade three, four stuff.

SPEAKER_00:

Exactly.

SPEAKER_01:

Ross frequencies catching up with breast cancer there, Kate.

SPEAKER_04:

Yeah, so I was just contemplating, too, if you've got a patient, what did you say, 70 something percent of patients with you for eight years? That means you'll have a significant length of people who are with you for longer. You are effectively their family physician. Yeah, you you have got more of a long-term relationship with them than than many general practitioners are able to provide, and in at least in New Zealand, I don't know what Australia systems like, uh, through no fault of the GPs, right? And that carries worry for this medical oncologist who struggles to keep up with uh oncology data, let alone what's the right thing to do for blood pressure. So yeah, I think that's that it's huge, isn't it? How we absorb that number of people and and and who is best to care for them and how for decades. And what happens when you retire? You know, all of a sudden you have to say goodbye to all these people who you know have been hanging off every word for years.

SPEAKER_00:

Doing how it works. Yeah.

SPEAKER_04:

Yeah.

SPEAKER_00:

All right. So we go on to some lung cancer.

SPEAKER_04:

15 years ago, 20 years ago, when I started drug oncology, lung cancer, we would have been like, all right, sweet. Take two minutes. We're still doing platinum doublets. But what exciting new stuff have you got for us to do that?

SPEAKER_00:

Incredible, because it's we know lung cancer is about 30 different cancers at least, isn't it? They all just start in the lung. So this this is going to be Cook's tour through some really incredible results with new molecules in these subsets of lung cancer. So first one's extensive stage lung cancer. So, Kate, what's the median survival of patients with extensive stage lung cancer that you were taught as a medical student? Do you remember?

SPEAKER_04:

Small cell? Yeah.

SPEAKER_00:

Oh, it's like six to nine months, right? Yeah, right. So this is now that's now getting blown out of the water. So we know that the standard of care now is chemotherapy plus uh immunotherapy, and develop is considered the standard based on previous studies. So this study was done in China. So this is the Delphi 303 study combining Talatamab, which is a bi-specific T cell engager previously shown to be effective in secondline uh therapy, or as first-line maintenance with a PDL1 inhibitor. So this was said to have manageable toxicity, but they had cases of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome or ICANNS, which was said to be mostly low grade, and only six percent of patients discontinued treatment due to an adverse event. So I wouldn't call that low grade. And predictive biomarkers may be required to tease out those who really benefit. But this agent showed an overall response rate, 73.3%, median progression free survival of six months, and 12 months and 24 months overall survival of 68 and 59%. So you have more than half the patients living two years compared to our kind of standard of six to nine months.

SPEAKER_01:

So while Craig, and how much of that is down to patient selection, how much of that is due to the age of the company. Oh, that's right.

SPEAKER_00:

Because it's a phase two study.

SPEAKER_01:

Phase two, right? So you don't have a comparative arms, that's the problem, isn't it?

SPEAKER_00:

But I'm just wondering tease out because these are these new drugs that are coming through China, there's biotechs, and they look to be highly active, and where they actually fit in the treatment um paradigms remains to be seen with future studies, especially based on those phase two results.

SPEAKER_01:

So, Craig, uh in New Zealand we don't have access to biospecifics in metaquoncology. I think the hematologists may have some, but we don't have any in metachoncology. Are they available in care in in Australia at all?

SPEAKER_00:

I don't think any are PBS listed, but there's certainly um many, many clinical trials in with uh biophasic monoclonal antibodies.

SPEAKER_01:

So the major centres will be starting to get some experience with these now in Australia?

SPEAKER_00:

The regional centres as well.

SPEAKER_01:

Regional centres as well.

SPEAKER_00:

And the larger regional centres that have the capacity and capability to manage those side effects.

SPEAKER_01:

Yeah, and I guess if you're doing um the CAR T cell therapy, the managing the, you know, having the team of expertise to manage the cytoclone release syndrome is that you're more familiar with, and so the drugs can be delivered more safely. And that would be something that I'd be worried about in our local environment, for example, where we just don't have that kind of experience or backup to to manage that. There's a whole new class of molecules that do require specific expertise to handle safely, right?

SPEAKER_00:

Yeah, but that's I mean that's that's always been the case with all you know medical oncology clinical trials. Like everything you're doing is new with new drugs is new, and you need to learn in the side initiation visit how to manage the side effect, and you look at the well, you look at firstly at the feasibility and whether you've got the systems in place to manage it before you sign up for the trial. You trained, you follow a protocol with tables with how to manage the toxicity, there's medical monitors available. So, you know, that's why trials are safer than probably just when the drug comes to market and you then you have to learn how to use it. Being involved in the trials gives you that hands-on experience and safety net, I think, to to learn how to use these new drugs.

SPEAKER_01:

And that's a really good point about and one of the advantages of doing clinical trials, right? In terms of developing local expertise in a structured and safe way. I think that's a really good point. Yeah.

SPEAKER_04:

But but I think also that we have to think of these as uh packages. So the management of potential toxicities has to be an important part of any, hey, this new cool drug is funded. I want to give it. Have you got the appropriate setup to be able to look after the patients? I love the science of these. Hey, T cell, meat, cancer. It's it's fantastic. You know, this is my skill set as introducing people. So I feel I feel kinship with these molecules. I also cause confusion and discompobulation amongst people I'm trying to help.

SPEAKER_00:

So yeah, yeah, but that's why this is a new thing, ICANNs and CRS. So I presume you guys use EVQ. EverQ's become the Australian.

SPEAKER_04:

Yes, and they do actually they do have a link, yeah.

SPEAKER_00:

Yeah, they do. So, I mean, that's the one-stop shop for how to do things, how to deliver drugs, how to manage the side effects. And so again, there's good treatment guidelines and algorithms in there, contextualized for the supportive care drugs that are available in Australia, you know, teaches you how to manage patients. And we ram home to primary care physicians, ED physicians, you know, that's the one. If they remember anything from our talks, you know, use the EQ website, you know, it's easily available on any computer or phone, and you can look up, you know, about the drugs and what to do.

SPEAKER_04:

All right, rapid fire, Professor.

SPEAKER_00:

Okay, rapid fire. Quick boats. Yeah, we'll stop asking questions.

SPEAKER_01:

We'll just start hickling now.

SPEAKER_00:

So uh late breaking abstract four, harmony six out of China. First line, Ivoneschamab plus chemotherapy, improving progression feed survival in squamous non small cell lung cancer. So this is a biphasic PD1 VEGF was combined with chemo compared to tisalismab and chemo. So remember, we used to use bevisimab sometimes for squamous cell cancer, none of there was a lot of trials done. Um, so this is a biphasic um PD1 VEGF inhibitor with interesting results in this population. The duration of response 11 months versus eight months for the tISLISMAB chemo hazard ratio for progression pre-survival 0.55. So again, the the criticism inevitably was this is in the China alone population, the study need to be repeated, and it's just probably a small clinical benefit.

SPEAKER_01:

So, but Craig, with the biospecific antibodies, uh why is that fundamentally different than just combining two drugs? I mean, they're comparing it as a lithmab to a PD1, VGF biospecific. Why aren't they comparing it to a Tizo with a Vestin, for example?

SPEAKER_00:

Well, they probably could, but that wasn't an arm of the study.

SPEAKER_01:

Do you think fundamentally that the biospecifics are different to combining two drugs?

SPEAKER_00:

Yeah, I know. It's a good question. I would guess it's probably in theory, you know, it's they're interacting in the tumour environment together. I don't know. Chris, do you know?

SPEAKER_01:

No, I don't. I'm genuinely interested because I think part of the problem is that studies are done by companies with a view to patent life, okay? Of course, that's that's capitalism, that's how they work. But you're not getting a fair comparison of you know, PD1 versus PD1 with VGF. You know, that's to me that design of that study. But what they're doing is PD1 versus Biospecific, which is PD1, VGF, as opposed to doing PD1 VGF with biospecific, PD1, VGF. So not really testing the innovation of the biospecific. I I don't I don't think it's a genuine comparison. And that's where academic group studies become more important, I guess, isn't it? Where they do ask those more meaningful questions. And it's difficult to invest money in RD if you're not gonna get a return on it.

SPEAKER_00:

Yeah. So they're great. Maybe there needs to be biospecific versus the two drugs individually.

SPEAKER_04:

Yeah. No, I think services mab alone is not gonna create that difference. Right.

SPEAKER_01:

No, not in the same, but in perhaps in combination.

SPEAKER_04:

Professor?

SPEAKER_00:

One of our favourite new drugs in like breaking abstract five, the optitrope lung O4 study, Sacetuzimab teroma T can. I think we've had sassetuzimab teroma TCAN. We've had other sassitudzimabs. This is for pre-treated EGFR mutated non-small cell lung cancer. Uh so the standard there people failed EGFR inhibitors would be chemotherapy in this study following progression on EGFR tyrosine kinase inhibitors, a progression free survival of eight months versus four months has a ratio of 0.49. Overall survival not reached versus 11 months has a ratio of 0.6.

SPEAKER_04:

Um Craig will kick himself when he hears when he hears this back to himself because he did just say patients fail therapies. Patients don't fail therapies, therapies fail patients, but but it comes out of our mouths all the time. You did just heavy. I know you're you're always having me on about it. You'll hate it.

SPEAKER_00:

I apologize for that. So um there was clearly a subset of patients that didn't appear to derive benefit, so we need more biomarker driven refinement. And it was well tolerated with no unexpected or critically limiting adverse events.

unknown:

Bing bing.

SPEAKER_00:

And it was done in China, so maybe need to be repeated outside of the Chinese population. Bing. According to the discussion.

SPEAKER_01:

It just goes to show how many studies are coming out of there, right? That's a huge number.

SPEAKER_00:

Yeah, clearly an amazing pipeline. I think it's probably dominant pipeline now. And then very quickly, two negative studies, the Dreamer R3, which was an Australian-led study in mesothelioma, looking at the role of addition of devolumab to chemotherapy in treatment of mesothelioma. So in the past, it's suggested to be benefit, but there was an underrepresentation of patients with epithelial disease. And this was a study that mostly had patients with epithelial disease, needed to be stopped early because of poor recruitment. But it was essentially powered enough to show that there was no significant difference in overall survival or median survival. And the other negative study, I think it's important that we do mention some negative studies. This was skyscraper O3. This was building on the back of the specific trial which showed that adding devoluumab to chemoradiotherapy was the standard of care in patients with unrespectable stage three disease. And this was a trial that wanted to take that approach, but add a digit inhibitor tiragolab.

SPEAKER_04:

Terra volumab.

SPEAKER_00:

It showed no benefit. So the d the the conclusion was better biomarkers are needed. So they weren't ready to throw the they weren't ready to throw the drug out of the pipeline, but they went down the better biomarkers are needed route.

SPEAKER_04:

So my two reflections on that is I'm surprised they haven't given up on Terragolymab yet, because it's been a lot of negative stuff. And the second one is mesothelioma is lungs pancreas, isn't it? It's just heartbreakingly sad. They try and try and try and we just can't. Thankfully, we may have seen the peak of meso now that the asbestos exposure is falling.

SPEAKER_00:

So that's it. Interesting ESMO for lung and GU.

SPEAKER_01:

What do you think you'll do differently as a result of this uh ESMO, Craig?

SPEAKER_00:

Well, I think the perioperative uh bladder cancer study may change practice if those drugs are available. I think like to have some uh clinical trials available with some of those other new agents in lung cancer. I think you would consider ensolutomide for that small niche of men who have rising rapidly rising PSA but no evidence of metastatic disease. But you have to individualise that and it's a discussion of risks and benefits.

SPEAKER_01:

And the thing is with the ensalutamide study, that agent's already widely available, right? And so that group will probably be receiving that treatment this week.

SPEAKER_00:

ENSA is available in that population. There is a slight difference in the PBS in Australia. They have a 10-month doubling time. The study was nine, so that's neither here nor there. And there's other agents available as well.

SPEAKER_01:

And what about you, Kate? What do you think will be practice changing for you as a result of ESMO?

SPEAKER_04:

Look, I will be discussing Matterhorn, so perioperative immunotherapy alongside Flot. I still will not be discussing adjuvant CDK46, but I do think if I treated lung, I would at least discuss the adjuvant TKI data. I think we're missing a trick with that. I think it's just suppressive therapy. And we're we're getting it into people before they get too sick when they relapse. But and if it was cheap, then I'd be giving it as a treat it like tamoxifen, I'd give it to everybody. I wouldn't have a problem with that at all. But it's just that they're not cheap.

SPEAKER_01:

Anyway, that's that's my uh very expensive. And of course, the uh pregnancy and breast cancer study as well.

SPEAKER_04:

Yeah, no, that that's very exciting. So it is safe to have a baby after a breast cancer diagnosis. That's really important, even if you have to pause your endocrine therapy.

SPEAKER_01:

Yeah, I think that's um massive. And and like you, I thought um D flot was again probably practice changing for most people in that uh tumour type, adding an extra six to seven percent is what the third big advance we've had in period of management of gastric cancer in the last uh 15 to 20 years. So I think that's a really big step forward that'll change our practice. Uh I agree with you, the breast cancer study will be really informative to an important group of people. And um and I think enzymide as well, Craig, I think, given that it's a really available well-known drug, will fast forward things and it'll connect into the clinic quite quickly too. I'm really interested to hear feedback already on the melanoma nine, your overall survival data as well in the adjunct setting of um NEVO versus high-dose uh IPI. You know, given that central lymph node biopsy positive melanoma is still a very common situation. How are people going to interpret that lack of overall survival in that stage three situation, whether or not people are gonna consider the lack of uh overall survival important when you consider the uh the morbidity of of relapse? Certainly it's a conversation I've already had in clinic with people a couple of times already. So, certainly a lot to come out of this uh ESMO. It's been a really good uh ESMO, I think. There's been a lot of new trends coming with uh biospecific antibodies and also a lot of good studies seen coming out of mainland China. We're gonna have to watch them as a rising power in terms of drug development uh and the power of uh Chinese pharma, particularly, for example, the UK is having a lot of problems with the drug environment, and so pharmaceutical companies are leaving uh the UK at the moment. So the landscape is is certainly changing uh out there now. It's great to have such an informative uh conference which influences our practice so much.

SPEAKER_00:

What's the change in the UK, Chris?

SPEAKER_01:

This was a Lance at oncology recently, whereby a couple of drug companies have said that they will leave the UK if they don't up the reimbursement for uh drugs, a drug price in the UK. And I think two companies already have said they're looking to leave the UK, so that could be potentially very significant. I would need to go back and read the article before I would use names of those companies on a podcast, but uh that's impactful if companies aren't getting revenue. They're disinvesting from a market in terms of RD. Okay.

SPEAKER_00:

And I think there's been some regulatory changes in Europe as well, which I've heard makes it less attractive to do work there as well. And so there's an expectation that there'll be significant pivot to Asia Pacific, actually.

SPEAKER_01:

I think so. Meanwhile, New Zealand continues to try to shoot itself in the foot uh when it comes to drug development and uh the environment to uh deliver clinical trials. New Zealand has the opportunity right now to position itself once in a generation of being New Zealand Inc. single point of entry for clinical trials, and they are doing their best to stuff it up. Uh so there's a number of people out there at the moment trying to unpick that destruction. Uh good luck to them.

SPEAKER_04:

Oh, so Chris, uh, that's Esmo in the back. What are you looking forward to next?

SPEAKER_01:

Well, it was a couple of good things. Um, speaking of the rise of China, um, I'm heading to the Chinese Anti-Cancer Association meeting in a couple of weeks. And after that, I can't wait for London Global Cancer Week.

SPEAKER_02:

And with that in mind, CJ, here's your pre-conference interview with Susie Stanway.

SPEAKER_01:

So, and with Susie Stanway, who is the uh co-convener for London Global Cancer Week. Good day, Susie. How are you? Good.

SPEAKER_03:

Thank you very much for having me on.

SPEAKER_01:

Good. So, how long has London Global Cancer Week been around for?

SPEAKER_03:

So it's a meeting that's running this year for the seventh year in a row. It started in 2016 as an annual day meeting, which we ran for all three years at the World Society of Medicine. And then Mark Lodge came along and saw what it what it could be due to the interest that we'd had in in what we were doing, and then became a week of meetings, which this year will be held um between the 24th and the 28th of November, and will hopefully feature between 50 and 60 hosts talking about what they're doing.

SPEAKER_01:

So are they hosts from all over the world or is anyone actually for you get together in London?

SPEAKER_03:

So it's mainly a virtual platform, which we feel is important to democratize access, both of those presenting and those attending. And we want to hear from people who are um who are affected and from a uh a a wide range of people from around the world across the cancer continuum, and also from people doing interesting work around the sort of cross-cutting domains of what effects' ability to improve cancer outcomes.

SPEAKER_01:

So, what sort of events would people expect to see during global cancer well?

SPEAKER_03:

So there will be some events which detail sort of traditional things that you might see at an international cancer meeting, so maybe some latest data presented. But I think the important thing about this meeting is that we appreciate that the majority of the world's cancer deaths happen in low middle-income countries. And we want to make sure that that these people that are mostly affected have a seat at the table and that we hear from them and that we learn from them. So I think that there's huge amounts that we can learn from each other. I want to hear about what interesting work is going on around patient navigation in Nigeria so that we can take those learnings and um import it into our country. I want to hear from people that might not otherwise be able to get to other um international cancer meetings either by virtue of the fact that they can't get a visa, it's challenging, or that they haven't got financial resources to attend these meetings.

SPEAKER_01:

Yeah.

SPEAKER_03:

So I think it's basically about that. It's about hearing about what really matters, hearing from the majority of the people around the world that are affected and making sure that it sort of creates space, I suppose, for holistic discussions and improves coherence in global cancer policy making and shifts this sort of issue of cancel up the development agenda.

SPEAKER_01:

So, whereabouts can people find more information?

SPEAKER_03:

So we have a website. If you just Google London Global Cancer Week, you will see. I think another of the USPs of this meeting is that it's free to host a meeting, it's free to attend a meeting due to the different time zones, because we hope that we appeal to people around the world. Meetings are recorded so people can attend and watch retrospectively if they're interested in something. And it should be a really interesting week. And we're most grateful to the people that take time out to get involved and people that that tune in to listen.

SPEAKER_01:

So a free meeting, uh, Cavern, Global Oncology Kids, uh hosted Lows here online that was available either uh at the time or uh let it download and learn about what sort of kids control initiatives they're happening from all around the world. Sounds sounds pretty cool.

SPEAKER_03:

Yeah, no, it's it's really exciting. And you know, we want to hear from we want to hear from multilateral institutions and what's happening at the global level, but we also want to hear about incredible things that are happening that you might not otherwise hear about um and how we can all learn from that.

SPEAKER_01:

Okay, so go to your favorite search engine and uh check out London Global Cancer Week and we'll put a link to that in the show notes too. Uh thanks for coming along and all the very best for this year's meeting.

SPEAKER_04:

Thank you so much. Awesome. Craig, what's on your agenda?

SPEAKER_00:

Oh, to go and have a lie down after going through all those abstracts, I think.

SPEAKER_04:

It's always lovely to share some time with a Kamatua, so elders of our of our group.

SPEAKER_00:

Sorry, Craig.

SPEAKER_04:

That's a bit legitimate respect, Craig. It was very much, and I'm still just in my 40s, so I will lord it over you.

SPEAKER_01:

Um just 40, Craig. Okay, that's right.

SPEAKER_04:

Yeah, only just only just and then uh in my own, I'm starting to gear up for San Antonio. So first time I've been away for a long time to Texas. Please let me in, and I'm really looking forward to that. Anyway, what a wonderful long episode that was. Chris is gonna go off to another meeting. Craig is gonna have a lie down, and I might have my dinner now, I think. So uh matuana, everybody.

SPEAKER_01:

Tanakwe.

SPEAKER_04:

Tanakwe.

SPEAKER_02:

Bye bye bye. Thank you for tuning in to the Oncology Journal Club Podcast, proudly brought to you by the Oncology Podcast, part of the Oncology Network. For healthcare professionals seeking regular news updates and insightful discussions, we invite you to join our community at oncologynetwork.com.au. Your free registration includes a complimentary subscription to our weekly publication, the Oncology Newsletter, a valuable resource to stay updated on the latest advancements in the field. We value your input and welcome your feedback and paper recommendations via our social media channels, email, and websites. Your insights help shape the conversation and drive the direction of future episodes. This is Rachel Babbin signing off for the Oncology Journal Club podcast.