The Oncology Podcast

The Oncology Journal Club Episode 8: Older Patients, Endometrial Cancer, Sarcoma in Brazil and much more

• The Oncology Network • Season 2 • Episode 8

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Curious about the latest breakthroughs in oncology treatment? Prepare to have your perspective shifted and hopefully a few laughs too, as we dissect the most compelling research and clinical insights with our expert hosts, Professor Craig Underhill, Dr. Kate Clarke, and Professor Christopher Jackson. 

Today’s episode covers an eclectic mix of papers from many different specialities. Craig tackles ASCO non-small cell lung cancer recommendations, sarcomas in Brazil and cardiovascular risks in cancer patients.

Kate dives into endometrial cancer, the HIMALAYA study and CAR-T.

CJ looks at colon cancer, pancreatic cancer and pain management. 

And a shout-out to our Series 1 hosts Professor Eva Segelov and Professor Hans Prenen who both have papers in today’s episode!

For papers, bios and other links visit the Show Notes on our website.

For the latest oncology news visit www.oncologynews.com.au.

We invite healthcare professionals to join The Oncology Network for free - you'll also receive our free weekly publication The Oncology Newsletter.

The Oncology Podcast - An Australian Oncology Perspective

Rachael Babin:

Welcome to the Oncology Journal Club podcast, a fun and educational oncology learning resource for medical professionals. I'm your producer, rachel Bavin, from the Oncology podcast. I'm joined by our esteemed hosts Professor Craig Underhill, dr Kate Clark and Professor Christopher Jackson. Today's episode covers an eclectic mix of papers from many different specialties. Craig tackles ASCO's non-small cell lung cancer recommendations, sarcomas in Brazil and cardiovascular risks in patients with cancer. Kate dives into endometrial cancer, the Himalaya study and CAR-T. Cj looks at colon cancer, pancreatic cancer and pain management. And a shout out to our Series 1 hosts, professor Eva Segalov and Professor Hans Prennand, who both have papers in today's episode. For additional insights, links to the papers and bios of our hosts, visit the show notes on oncologynetworkcomau. The Oncology Journal Club podcast is produced with pride by the podcast team at the Oncology Network. Thanks for listening.

Craig Underhill:

G'day. Welcome everybody to episode eight of the Trans-Tasman Across the Ditch OJC podcast. We've all just got our heads around all the information from ASCO. It was quite a big meeting this year, wasn't it? Probably quite a few practice changing things, and we'll touch on that and then get into some new information. How are you going, Kate?

Kate Clarke:

Very well, beautiful day in Wellington today. As always, poor old Craig wanted to know what the light was coming in the window.

Craig Underhill:

And Chris, how are you?

Christopher Jackson:

going. Kia, ora, look, I'm doing really well. Thanks very much. I've got myself a brand new pooch, a little wee Cavoodle called Alfie, and Cavoodle of course is anoodle. Of course is an australian brand um of doggy uh, and I absolutely love them. My first doggy ever in my entire life.

Craig Underhill:

I have no idea why you brought that up, but anyway we'll just go straight.

Christopher Jackson:

It's important, exciting event, my life craig you know I like to share with the audience what's going on in my life, and if you do hear some barking in the background, it's for the latest podcaster.

Craig Underhill:

Okay. So, kate, what have you got for us this episode?

Kate Clarke:

So I want to put a caveat on this presentation. I no longer treat gynecological cancer, but I do find it fascinating when you read stuff papers from other people's subspecialty. You wonder how the thinking in each subspecialty is so very different. So you'll all recall that we're very excited post ASCO and continue to be very excited about single agent or double agent IO in DMMR, colon and other GI cancers. We've chosen, or the colorectal community has chosen to not do chemo plus IO, They've chosen to do IO alone, has chosen to not do chemo plus IO, They've chosen to do IO alone.

Kate Clarke:

In endometrial cancer, at least in first line the data was all chemo plus IO and there are stonking hazard ratios compared with chemo alone. But I feel like there's a missing arm, Although all the second line data is single agent IO. So both the Ruby and NRGGY018, so Ruby being chemo plus distalamab, NRGGY018, which needs a sexier name, is chemo plus Pembro have very similar hazard ratios in the DMMR group and intriguing non-significant hazard ratios for both PFS for both and OS for the Ruby trial in the PMMR group. So I'm really just putting a question mark to cleverer brains than me as to why we still don't sit down as a community and talk about our findings amongst each other, and are we missing out on good strategies as a result?

Craig Underhill:

Thoughts- yeah, you're talking, then, about the issue of super subspecialization versus general medical oncology. I think that's right, kate. I think you see, when you're coming across feasibilities or discussions about new protocols in a certain tumor type, being in regional and being involved with more than one tumor type, you can see that sometimes perhaps the lessons learned from one tumor is not necessarily translated across type. You can see that sometimes perhaps the lessons learned from one tumor is not necessarily translated across, and that's probably the important role of medical liaisons within pharma companies and people within non-pharma cooperative groups to transfer that knowledge. So, as you say, in colorectal space, single agent IO has been shown to be pretty effective in early studies with not long follow-up. So it's intriguing that in the endometrial space it's gone with combination chemo rather than just single-agent IO. So it's a good comment and good hypothesis. So maybe it's almost a standalone specialty, isn't it now, gainey? Maybe that's one of the issues there.

Kate Clarke:

I am curious. I'm curious, particularly as I know as a GI oncologist. I don't think Kapox is particularly toxic, provided you watch the oxaloplatin. But carboplatin-pactitaxel comes with peripheral neuropathy needing a lot of pre-meds alopecia. You know, yeah, chris is raising his eyebrows, meds alopecia. You know, yeah, chris is raising his eyebrows. You know, uh, in a group that are all and and it is a disease, uh, of the older and the infirm uh.

Kate Clarke:

So I'm curious as to why there isn't a third arm in those trials, and there may be some biological rationale, but it is not discussed in any of the papers that I've read, and I'm I am just really curious. So if there are some gynecologists who know more about this stuff than me, I'd love to have it explained to me. I'd also like to understand whether the signal that we're seeing in endometrial cancer is driven by another biomarker we haven't picked out yet. In the PMMR groups they are getting responses that we do not see in other disease types, although there are pole mutations in endometrial cancer. My endometrial cancer colleagues reassure me that the chances of those going to stage four is very low because they do so well. So I'm fascinated.

Craig Underhill:

Okay. So, kate, you said something intriguing there about Kapox was not toxic or something, so that looks like a segue. Actually, that's a set of oh yes, going into now Chris's paper, which is about oxali-based adjuvant chemotherapy in older patients with stage 3 colon cancer. So let's see what Chris has to say about K-pox.

Christopher Jackson:

Just choking on something there, thinking that Kate's saying that K-pox is a toxic regime. I think you should ask our charge nurse on our ward if K catpox is a toxic regime. I think you should ask our charge nurse on our ward if catpox is a toxic regime and she'd probably say yes, based on the length of stay that people have on TPN from that combination. Nonetheless, the long bite I wanted to talk about today was Oxyliplatin, stage 3 colon cancer, an analysis from the Accent Idea pooled database from the 12 trials. Of course, accent was the brainchild of the late great Dan Sargent, who had visited AGIDG Australia a number of times, was a great servant of the GI community and is sadly missed. Idea and ACCENT, people will remember, was an international collaboration where they analyzed 12 adjuvant studies of six months versus three of oxaliplatin-based fluoropropanine-based chemotherapy in stages two and three, predominantly colon but also occasionally rectal cancer. The headline from that study was that, effectively, three months versus six was about the same Maybe in the high-risk groups it was 1.4% difference but 30% more toxic for six months oxaliplatin-based therapy. There's been this big question mark, though, hanging over patients aged over 70 years of age with oxaliplatin. If you look back at the original Mosaic study and even the NSABP CO7 study, which was bolus 5-SU versus bolus 5-SU with oxaliplatin. When you looked at the subgroups, those over 70 never actually had a significant survival gain from oxaliplatin at all. Their time to relapse was about the same, but their overall survival was shorter in the over 70 age group. So the question of whether actually oxaliplatin adds anything in the over 70s has actually been a bit of an open question. If you're an evidence-based stickler you would say there is no evidence for benefit of oxaliplatin in the over 70-year-olds. But most people would still use oxaliplatin in stage 3 colon cancer still, as I say, actually without strict evidence. Also, the other thing is that oxaliplatin doesn't actually add all that much, despite the fact that it is standard of care in stage 3 colon cancer. The DFS gain is good 5% to 8%. That's a good additional gain, but the overall survival gain in mosaic is only actually 4%. So it's actually quite limited and given it can cause up to 30% neurotoxicity, grade 3 at six months, it's very relevant to shorten the course. So why might the over 70s be a different subgroup? Well, over 70, you get age-related immunosinnescence and age over 70, you have oxaliplatinism and immunomodulation as much as it is a DNA double strand breaker, so that might be a mechanism. Patients over 70 may have increased toxicity due to changes in distribution of body fat and changes in sarcopenia. And, of course, people over 70 may have additional comorbidity or frailty that's not there in those under 70. Now, when the average age of diagnosis of colon cancer is 67, this is actually a really important question for the majority of people with bowel cancer. So that's a preamble On to the study.

Christopher Jackson:

This is a pooled analysis looking at differences in toxicity and outcome data in those aged younger or older than 70. 12 studies, more than 17,000 patients the largest cohort we've actually got. They looked at does dose intensity actually partly explain the lack of efficacy and is dose intensity different between those groups? The three key endpoints they were looking at were time to relapse, which was the time from randomization to relapse, and if you died of something other than colon cancer, that didn't count. Dfs, which was recurrence or death, so if you had a toxic death, that would count. And overall survival.

Christopher Jackson:

And they looked at the early treatment discontinuation and early oxaliplatin discontinuation between two arms and overall grade three for toxicity. What they found was those patients aged over 70 were more likely to discontinue oxaliplatin chemotherapy or chemotherapy prior to receiving 75%. So over 70s had 22% discontinued early compared to 15% under 70. And oxaliplatin was discontinued early in 42% of those aged over 70, compared to 33% of those aged under 70. The relative dose intensity was about 7% lower in those over 70 compared to 33% of those aged under 70. The relative dose intensity was about 7% lower in those over 70 compared to those under 70. So those are actually quite interesting margins in terms of exposure to that.

Christopher Jackson:

In terms of toxicity, there wasn't any major difference except for grade three diarrhea, and grade three diarrhea is more than seven loose motions a day requiring intravenous fluid, and usually when you get that with capcitabine you're in hospital for one week, two weeks, some of the TPN. Occasionally you've had patients with toxic mega who need major surgery. It is a debilitating complication, grade three diarrhea in people with capcitabine, and it goes from 11% to 14%, which is meaningful. It's a difference between one in 10 versus 1 in 6.

Christopher Jackson:

In terms of efficacy outcomes, well, it's not an oxaliplatin versus not study, but what it did show was that, even though the time to recurrence was no difference in those under 70 and over 70, the overall survival and DFS was 7% worse if you were aged over 70.

Christopher Jackson:

So our older patients are doing worse. They are getting a little bit less chemotherapy, but the chemotherapy toxicity profiles are broadly similar. It does not necessarily explain the differences in overall survival and whilst it provides some toxicity reassurance, I still don't think it's put to bed the question of whether we should be giving Loxalipatin routinely to those aged over 70. So I think it remains a legitimate discussion. Six months capsidobin alone versus three months capox for those over 70. And evidence-based ticklers will say no real evidence for oxaliplatin in that group, and I think that's true, whereas I think it will remain standard practice for many around the motu or around the country, around the land to continue to give that, even with questionable evidence. So there we are. What do you think, craig? Have I convinced you to reconsider oxaliplatin in your next 75-year-old with stage 3 colon?

Craig Underhill:

cancer. Well, it's difficult, isn't it? So does it age, or is it the function? So, again, we screen all our patients with a G8 score. We're still stuck in this kind of age mindset.

Christopher Jackson:

Is that because you're getting closer to the age cut point, craig? So you want to be considerate to the individual, possibly, you know, whereas Kate and me, being at least a generation younger, aren't so caught up on it?

Craig Underhill:

But you know that's an interesting question, isn't it? So yeah, I think everybody would give pause to using it in the over 70. They need to be pretty fit and probably 75 is probably really stretching it. So but your dfsos argument is interesting. There was a landmark analysis by the fda many years ago showing that three-year disease-free survival was in fact a reasonable surrogate for overall survival. Because, you know, sometimes we can't wait for the five-year overall survival to start making decisions and there is that element of crossover or people not actually getting the drug when they relapse. So you need to give your best drugs first. So I would think that the landmark Mosaic data still provides the standard of care for at least the under-70s anyway.

Christopher Jackson:

Yeah, look, I think that's right and I think this paper still holds up the DFS-NOS relationship. But the time to relapse is different to DFS. The time to relapse is only from diagnosis to relapse cancer and it excludes death from any cause. So as you get older you get competing causes of death, right. So competing morbidity, competing mortality. So you might die of cardiovascular death, you might die of anything else. But actually it's entirely plausible that oxaliplatin or other therapies actually accelerate cardiovascular risks. It's entirely plausible.

Christopher Jackson:

So I don't think you should discount DFS or OS as the endpoints in favor of time to recurrence. So I don't like time to recurrence because it excludes all causes of death. I do think you have to consider competing morbidity, competing mortality, particularly in adjuvant populations, because it is relevant whether or not it might accelerate some other risk factors. So DFS yep, I'll take that, and not silly platin colon cancer study every day of the week. It's been a well-proven surrogate. Not true for other diseases. But OS for adjuvant and other studies still remains the king. But OS4, adjuvant in other studies, still remains the king.

Kate Clarke:

Long live the kit, kate, would you agree? I do agree to some extent. I think this is where the art of oncology kicks in, because I think what Craig was alluding to is there are 45-year-olds and there are 75-year-olds, and some 75-year-olds look 45 and are physiologically close to 45, though I always tell them that even though they look good, their liver and their kidney are probably a bit tired. But I think it's interesting. I sat in a room where we were presented some cases that looked different on the surface but were actually very similar. They gave us five in a row and all they did was change the order of the clinical information and then change the age subtly to try and figure out where people's comfort is.

Kate Clarke:

People are increasingly comfortable with treating people under 75 as young people. Treating people between 75 and 79 is kind of a bias, but as soon as you hit 80, people are like well. So I find that really interesting and that's just a gut thing. That's because there is no data in what to do with people over 80. But Chris is right, an increasing number of our patients are properly old, at least on paper, yeah, and we have no data as to what's doing with them.

Christopher Jackson:

Yeah, I think that's right, Kate, and when you look at the differences between jurisdictions and projects like the International Cancer Benchmarking Project, which is comparing outcomes between high-income countries, some of the real differences in cancer stats are happening in that 75 plus, 80 plus age group. So there are some countries which are treating that geriatric population more aggressively, and so how the patients in their age group get treated in New Zealand may be different to how they are elsewhere. Patients are important to keep at the centre of everything, but there are some inevitable things that happen as you age, including, as you point out, renal function. Capsaicin is a renally cleared drug. Of course, polypharmacy and I think changes in body composition are actually quite relevant. People often assume that obese patients get more toxicity because they get higher dosing, but that's not true. It's the inverse People of low body weight actually get higher toxicity, and I think that probably is sarcopenia which does that right.

Kate Clarke:

Yeah, and there are some really, really simple interventions that we keep forgetting, which is that the more physically active our patients are while on adjuvant chemotherapy, the better they do, both tolerance-wise and disease-free, survival-wise, and we forget. So I am delighted that we're getting some ridiculous amount of money to spend on new drugs, but we don't have outpatient physio. So that's my little plug for my personal bias.

Christopher Jackson:

Yeah, I think that's right. Everyone should do CrossFit.

Kate Clarke:

Or just go for a walk. You don't have to join a cult.

Craig Underhill:

All right, I've got a few quick bites and a medium bite. So the first thing to mention is management of stage three non-small cell lung cancer. Asco rapid recommendation update published in the JCO in June. So in 2021, asco published their guidelines for stage three non-small cell lung cancer management and in 2023, they issued a rapid update and they've done another one on the basis of the phase three Laura trial, which was presented at the ASCO meeting. It was one of the kind of much discussed and landmarked meetings that we talked about in our ASCO update podcast.

Craig Underhill:

This was a study where we joked about you could drive a truck through the survival curves or the PFS curves. I should say so. This is a study in patients with stage three disease following concurrent or sequential chemoadiotherapy with an EGFR exon 19 deletion or an L858R mutation 2 to 1 randomization. Oral osimertinib 80 milligrams once daily or placebo, and there's only 20% purity for the overall survival data. But the PFS survival data was 39.1 months versus 5.6 months, with a hazard ratio of 0.16. I didn't mispronounce that 0.16. And so, on the basis of that, asco has gone ahead and recommended that that should be the standard of care for those patients.

Craig Underhill:

My next one is a paper from Brazil in the JCO Global, and so this is a discordance between the initial diagnosis of sarcomas and subsequent histopathological revision and molecular analyses in a sarcoma reference center in Brazil. And so in nearly 60% of cases the initial sarcoma diagnosis was modified when it was revised by a reference center and dedicated pathologist assisted by molecular pathology. So sometimes it changed from malignant to benign or the subcategorization of the sarcoma was changed. So interestingly, that was consistent with other data from Europe and North America as well. I think I just wanted to highlight that because I think it reflects probably contemporaneous practice in that people are referring sarcoma cases to a reference centre and if they're not, they should. Highlights that we need to continue to do some work in other less common cancers to really have some reference centers where at least pathology can be checked or MDT discussion can be held remotely and then components of care delivered closer to home. But I do look at the JCI Global from time to time and Eva Segalov, our former host, is an editor of that journal and they do have some interesting articles from lower and middle income countries.

Craig Underhill:

And then another one in. I know you're going to do some pancreas cancer short bites, chris, but I found one pancreatic cancer surveillance and survival of high risk individuals. So this was a comparative cohort study, not a randomized study. Patients with high risk. So these were people with a strong family history or a known genetic mutation predisposing them to developing pancreatic ductal cancer, where they were given surveillance versus previous controls, and they actually demonstrated at five years, a lower mortality rate in the high-risk individuals compared to the controls of 43% versus 86%, and the high-risk patients lived longer than the matched controls, with a median overall survival of 61 months versus eight months and the five-year overall survival rate 50% versus 9%. So it's an interesting study. Kato, chris, in your practice, in your centers, would high-risk individuals be undergoing surveillance for pancreas cancer?

Kate Clarke:

No, I'm curious as to what the surveillance methods were.

Craig Underhill:

They were some ultrasounds. It was endoscopic ultrasound and MRI, wasn't it, craig? Just looking at the detail, it looks like they got either CT or MRI or endoscopic ultrasound, so it looked like it varied between institutions. It was done across eight sites.

Kate Clarke:

You know when the alternative is a Whipple for many of these families if they really want to reduce their risk, then it's easier to justify heavy surveillance. But I'm curious as to anybody is offering an age-related, age-specified Whipple as a third option. So you've got your, don't do anything. Survey very heavily, and would anybody put their hands up?

Christopher Jackson:

Some of these families have almost a guaranteed risk of pancreatic cancer disgusting disease that it is, yeah look, I mean, I think people who've got familial cancer syndromes or very high risk cancer are very interested in this. You know, and I think the way in which MRI is going, in particular, looking at whole body mass too, you can actually do screening for multiple sites all at once, so there are a lot of advances there. I'm not sure that standard CT in this would be an awesome idea. People have already got DNA repair problems exposed to ionising radiation, so I think you don't really want to do that with non-ionising techniques like MRI or, alternatively, with EUS, and EUS is not non-morbid. But I think if you're looking at people with BRCA1, brca2, they could be highly, highly motivated individuals to undergo this type of screen at grey.

Kate Clarke:

Yeah, I was talking more at the higher end, in that BRCA1 and BRCA2 have a significant risk, but there are other familial syndromes that their pancreatic cancer risk is. Their relative risk is 88 times the baseline risk. You know we're talking ridiculous. I think it is really difficult to in New Zealand practice to get young patients with pancreatic cancer to see genetics in a way that it's not tricky to get young patients with breast cancer or ovarian cancer to see genetics, even though we know that the pickup for people, even without a family history with pancreatic cancer, for somatic genetic mutations is very high, much higher than a young triple-needle breast cancer woman, for example. And there's definitely some work to be done advocating for more equitable access to genetic screening.

Craig Underhill:

So, chris, you've got a couple of short bites.

Christopher Jackson:

Yeah, I was staying with the pancreas theme a little bit longer there, craig. A real problem in the management of people with advanced pancreatic cancer, of course, is celiac plexus nerve pain, which is a really troubling and debilitating symptom. For many People end up on opiates, on urolytic agents like gabapentin sorry, membrane-sablizing agents like gabapentin or pregabalin, for example and it can be really difficult to control that pregabalin, for example and it can be really difficult to control that. You have access to celiac plexus neurolysis in many centres, particularly using EUS, and some people argue for two-directional EUS with neurolysis versus one. But like most of these palliative measures, the evidence basis for the intervention is actually quite poor and the randomized data is not very good.

Christopher Jackson:

I just wanted to highlight celiac plexus radiosurgery for pain management in advanced cancer which had celiac plexus type pain. The things I liked about the study were that they used a standardized pain score in all of these patients and they said in advance what a meaningful, clinically meaningful reduction in pain score would be these patients and they said in advance what a clinically meaningful reduction in pain score would be. They then did stereotactic radiotherapy or radiosurgery to the celiac plexus area and they found a 53% reduction in pain by the pre-specified meaningful level, which is good to see palliative care type studies giving these types of standardized response scores. I think that if you looked at the same sort of data in bone metastases and used a similar pain score, you'd get a similar sort of response. So I think what you can say is that radiation to celiac plexus does give a similar level of benefit to that at which you would expect for bone mets. Whether it's better than celiac plexus neuralysis remains an open question. For bone mets, Whether it's better than celiac plexus neuralysis remains an open question, but it may not be as difficult to get in some areas compared to others, and so accessibility remains an issue for many of these areas. But I think it does give us some comfort that it's a good thing to do, or a reasonable thing to do, with an adverse event profile which is fairly similar to that what you'd expect in upper GI patients.

Christopher Jackson:

The other quick bite I've got today for you guys is really just an ode to our former presenter, professor Hans Prennen, world famous for his prediletation for papers in nature and nature medicine. He always used to like to do that. Anyway, hans, I hope you're listening. Man, this is a shout out just for you. We miss you.

Craig Underhill:

Hang on. We've got a special shout out, Chris, because we have a special segment called Blow your Own Trumpet. So this could be a blow your own trumpet from far away.

Christopher Jackson:

Well, we might have to get Hans on to answer some questions about this. I don't know if I'm blowing his trumpet, particularly I might be sticking a sock in the end of the cornet, but you haven't heard what I have to say just yet. Here we go, hans. If you're listening in Belgium, we're going to find out, waiting for the hate mail to come in. Anyway, this was a multicenter, single-arm phase 1B-2 study of combining a CD40 agonist with modified falferinox. Now, hans, did I get this right? Am I going to pronounce the drug name right?

Christopher Jackson:

Metazolamib, metazolamib, metazolamib, metazolamib, cd40 agonist. Why CD40? Well, apparently CD40 is a co-symmetry receptor expressed on the surface of B cells, monocytes, macrophages and dendritic cells. In the CD40 agonist, which is supposed to help the immunoreactivity and helps immunogenic cell death, they did a phase 1B-2 study, gave them falferinox plus a dose-finding study of this novel agent and if they got a response rate more than 35%, they said it was successful. They achieved their pre-specified response rate of greater than 35% and they said it was successful. Please got a randomised phase 3 study. They say Hans, man response rate in pancreas cancer 35%. Your response rate with falvorinox is 31% in multinational phase three. It's a pretty low bar and single arm phase 1B, slash 2 studies. They don't tell us anything about efficacy. Man, I'm not into this design at all. Come back on the show, defend your study.

Craig Underhill:

We might have to get him back in Metazolamab. Metazolamab and it's a CD40 agonistic IgG1 antibody.

Christopher Jackson:

That's it. Wow, it's a metazolamab.

Craig Underhill:

So not impressed with the activity.

Christopher Jackson:

Even though Hans is a dear friend of the show, I'm not a fan of single arm phase 1b studies with response rate as their primary endpoint, because they are super selected patient populations and response rate drops as you go from phase 1 to phase 2, to phase 3. And so going straight from a phase 1 to a phase 3 with this level of data, I think will be an expensive fishing trip. So, hans, randomize phase two first, please, before we go to the phase three.

Craig Underhill:

Okay, Thank you, Chris. I'm just waiting for the phone to ring now from Hans Kate. You've got a couple of quick bites for us.

Kate Clarke:

Yeah, just very quick. My first one is just a four-year OS update from Himalaya. So Himalaya, beautifully named, don't know what it stands for is the stride versus DERVA, versus serafinib in HCC. Remembering that these are very well hepatocellular carcinoma patients, they all have to be child's pure A. They got one dose of tremolimumab and then ongoing DERVA and although there was a DERVA single agent arm, everything was powered to compare with serafinib arm and the stride regimen, as it calls itself single trimolimumab and ongoing I can't remember the actual word. Devalumab did much better and the four-year OS is 25% versus only 10% in seraphinumab. So that's pretty exciting and they're going to do some work as to whom is most likely to be in that 25% so that we can have a think about it, because that's quite a cheap strategy compared with other ones where you keep going on the anti-cyslaphylaphore for ages.

Craig Underhill:

Kate, where would you put this regimen, though the tremolumab dervillumab, compared to, say, io and a TKI together?

Kate Clarke:

So standard of care quote unquote is probably IO versus an anti-VGF agent. It's, you know, tzob published first but nobody's done a head to head of IO and some kind of anti-VGF including TKI in that group versus this one. And I think that there's some advantages to not having an anti-VEGF agent in that you, by virtue of having cirrhosis many of these patients have clot, have varices, have other things that take them out of an anti-VEGF arm. I'd love to have access to this and I think you'd probably choose horses for courses, okay, Thank you.

Craig Underhill:

And then you've got a car T-cell.

Kate Clarke:

Oh look, this is just. This is my last one. So Rob Winecove is a mate, lives down the road and this is just a shout out to the fact that even in little old New Zealand real research is possible if you are and I hope Rob's listening bloody minded enough. So Rob has managed to do a phase one, first in human car Tcell in wellington. But just so you understand who, what, who, yeah, he's amazing. So he said who rob is.

Kate Clarke:

Rob was having a conversation with a mate about how it's fastest to go between the hospital and the university and so he did a multi-visit randomized control trial amongst himself. So he rode in a bike, he went in a bus and he drove in a car. Uh, and did it door to door to try and eliminate as many confounds as possible. The guy's just a born scientist. He's fastest to cycle in Wellington. So there you go. So this was a CAR-T. This is the phase one. They're moving on to a phase two. They want another 60 patients and in B-cell lymphomas relapsed or refractory. That's very hard to say. Pre-my glass of wine. Fantastically for a New Zealand study, 20% Maori participants, which is wonderful, and some fantastic responses, including many sustained, complete responses. So we're very excited by having this here. We're very excited by Rob driving this, and I'm also very excited to see some of the young people that he's worked with, including other local consultants and other advanced trainees, listed as significant authors on this paper. So yay, Rob, Way to go.

Craig Underhill:

And have you talked to him, kate, like where's this going? You think it's going. I mean, car T cells seems to be coming into play more and more in the relapsed refractory non-induced lymphoma. And is that what they expect with this particular version?

Kate Clarke:

Yeah, look, I think he's been really clever. So one of the things that he's trying to do at the same time is capacity build. So he's been building in an understanding of the toxicity reviews that require. So he has a relationship with neurology, he has a relationship with ICU, he has a relationship with our drug funding organisation in terms of tocilizumab. Yeah, he's really been thinking about that. How do we make this into a CAR-T programme that New Zealand can sustain internally? So I think at the moment relapsed refractory lymphoma moving into a larger group of patients, confirming his responses. But he's working with the malignant, which means that he has the control over the genetic design. So as we find more targets, he will be able to adapt these T-cells to attack those targets. So really exciting.

Craig Underhill:

Is there a CAR T-cell program anywhere in New Zealand?

Kate Clarke:

No this is it?

Craig Underhill:

Yeah, wow. So it's interesting because I learned today that the sixth program has opened in Australia in Townsville. You know that's a big university, comprehensive university hospital with most components of you know, oncological surgery et cetera. But they've just started a nascent CAR T-cell program there to enable access for patients in North Queensland. So which I don't know 3 million people in New Zealand. There's probably one and a half million people in North Queensland. So which I don't know. 3 million people in New Zealand. There's probably one and a half million people in North Queensland. Hopefully program will come up in New Zealand but at the moment people across the Tasman if they need to access this but it'll be very expensive for them.

Kate Clarke:

The most famous patient here who has been incredible and I apologize if anybody's listening can remember his name. He's a comedian. He went to the States to join a research program with his own lymphoma, raised a lot of money. By the time he got over there he got accepted onto a trial, didn't need the money. He donated all the money to the Maligan to help set this up. So this is a beautiful story and at some point the book will be written.

Craig Underhill:

Okay, fantastic. And then my last paper is another blow your own trumpet from afar. And then my last paper is another blow your own trumpet from afar, because one of the authors, eva Segolov, who is now based at the University Hospital, university of Bern in Switzerland, and she co-authored this with Sean Tan from the Victorian Heart Institute in Monash, and the senior author was Stephen Nichols, also from Monash, who we've had on the show. Eva did a whole podcast on cardio-oncology and I'll refer people back to that. We'll put a link in the show. It's still an interesting topic and worth thinking about.

Craig Underhill:

So this paper was in a journal called European Journal of Preventative Cardiology, which is the journal of the European Society of Cardiology, and it's called Cardiovascular Risk in Cancer Patients Treated with Immune Checkpoint Inhibitors Challenges and Future Directions. So it's a bit of a review, but authors making the point that as people are living longer with cancer, especially after the advent of immune checkpoint inhibitors in certain tumors, they're being put more at risk of cardiovascular events. So they actually stated that there's a growing body evidence around the risk factors for people receiving immunotherapy and so the atherosclerotic cardiovascular disease. There's some evidence from a retrospective study of 6,000 patients with a threefold increase in myocardial infarction and stroke following immune checkpoint inhibitor therapy. So that's quite a lot threefold. So we know about myocarditis as an acute onset, but because these are pro-inflammatory agents, it makes sense. We've known for a long time that there's a link between chronic inflammation, cardiovascular risk, and so they're making the point that, like with many other cancer treatments, we need to think about testing people for cardiovascular risk factors and managing that. And of course, we start getting into the space of do they have advanced disease and they're not going to do well, do we need to think about cardiovascular risk factors? But now we're actually curing people, or people are living for years.

Craig Underhill:

Whose responsibility is that? Is it everybody's responsibility? Is it medical oncologists? Is so the gp? Do we need to set up clinics? You know, refer to cardiology service. There's evidence that, as well as that, um, atheroscleric causes dyslipidemia. So there's a whole lot of there's a growing body of evidence. So we won't get too much into the discussion, but I think was just something for people to note that and think about. You know, as we are having more and more people surviving their cancers or living longer with their cancers, we do need to think about the whole person and thinking about those other risks that we might be exacerbating. So interesting paper.

Kate Clarke:

Yeah, I wonder if we're going to, as adult oncologists or oncologists of adult patients need to learn from the survivorship clinics that come out of pediatric cancer. We've had the luxury, or the lack of luxury, of not having a lot of long-term survivors, and now we're in another space.

Craig Underhill:

Yeah, kate, there's a service improvement project application grant application there. So I think it's a. You know this paper points out there's a whole lot more population-based research needs to go on, and researching new models of care, et cetera. So I think going forward we're going to see more and more attention in this space. So I thought it was worth the obscure journal for oncologists, but you know a topic worth noting and worth thinking about. Thanks for that, craig. All right, so on that note we will bid you all adieu. Thank you to everybody listening. Thanks Kate, thanks Chris and thanks Rachel on the sound desk there.

Rachael Babin:

It's a pleasure.

Craig Underhill:

And thanks Kate, and we'll see you all soon.

Rachael Babin:

Mate wa. Thanks, craig. 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 oncologynetworkcomau. 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 website. Your insights help shape the conversation and drive the direction of future episodes. This is Rachel Babin signing off for the Oncology Journal Club podcast.