The Oncology Podcast

The Oncology Journal Club S3E5: ASCO 2025 Special - Part 2

• The Oncology Network • Season 3 • Episode 5

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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

Welcome to the Oncology Journal Club ASCO 2025 Special – Part 2! This is where we take a famously different approach to oncology research.

If you're after an enlightening and entertaining take on this year’s ASCO meeting, the OJC team has you covered – blending expert analysis with trademark humour.

Our hosts go beyond the standard presentations to explore what the research really means for clinical practice.

For links to the abstracts and bios of our hosts, head to the show notes on oncologynetwork.com.au.

Subscribe to The Oncology Newsletter for regular updates on the latest cancer research and join our community at oncologynetwork.com.au.

The Oncology Podcast - An Australian Oncology Perspective

Rachael Babin:

Welcome to the Oncology Journal Club ASCO 2025, special Part 2. This is where we take a famously different approach to oncology research. If you're after another enlightening and entertaining, take on this year's ASCO meeting. The OJC team has you covered. Blending expert analysis with trademark humor, our hosts go beyond the standard presentations to explore what the research really means for clinical practice. I'm your producer, rachel Babin, from the Oncology Podcast, and I'm joined by our brilliant hosts, professor Craig Underhill, dr Kate Clark and Professor Christopher Jackson. You'll find links to all of the abstracts in the show notes at oncologynetworkcomau. This episode is proudly brought to you by the Oncology Network's podcast team. Thanks for listening.

Craig Underhill:

All right. Welcome back everybody to the second part of this post-ASCO special First episode, somewhat chaotic, interrupted by dogs and fire alarms going off, people burning toast and me struggling to understand Chris's accent. Welcome back CJ and Kate.

Christopher Jackson:

Bonza Craig, G'day mate, that's the way.

Kate Clarke:

Try to make you feel at home there.

Christopher Jackson:

Your bloody galah.

Craig Underhill:

It's like music to my ears. You're a funny Sheila Kate.

Christopher Jackson:

Fair suck in the sand, Chris.

Craig Underhill:

Yeah, great. Well, want to rip into some of the skin stuff for me.

Kate Clarke:

I was going to start with the pancreas just now, why not?

Craig Underhill:

Just because I've got my papers open at the pancreas, you're going with the chaos of this series.

Kate Clarke:

Go for it. Kate is going to wade in on this one Now. Over the years the Italians have been thoroughly overlooked. They've had this pancreas cancer regime called PEFG, so cisplatin, epirubicin, fluorouracil and gemcitabine. When you look at the response rates and the PFS and even the OS on there, it was always doing better than gemcitabine or gemcitabine capcitabine, and it wasn't that far off of furanose in their studies. But everyone seemed to ignore it and every time you went to a presentation on pancreatic cancer, unless it was a discussion by an Italian, no one would ever mention it. I can't quite work out why it got ignored so much. But anyway, they've moved on a little bit and from their PEFG they've now got PAXG. I've got to be careful. I say that right, craig, so you can hear the A, the PAXG, not the PIXG the PAXG, because the key difference from the epirubicin is a brexane and I'd hate for you to be prescribed with the wrong drug there. We've got to have the NAB Paclitaxel rather than the anthracycline there. So this is PaxG, which is a fortnightly regime of cisplatin, 30 mg per metre squared, so similar to biliary doses, pretty low Abraxane 150, which is about standard for a fortnightly dose. The X is for Zolota, which capsidabine, of course, 625 mg per metre2 BD, continuous, no interruptions, and gemcitabine 800 mg, which is quite low actually for a fortnightly dosing there, and that was compared to falfuranops with urinotecan dosing of 150 mg per m2. There was a second randomization to timing of surgery but they didn't report that and that's really not what the headlines are.

Kate Clarke:

The primary comparison was event-free survival. Now, event-free survival was a composite endpoint of progression, unresetability, intraoperative M1, or an increase in CA99 of more than 20% on two occasions more than four weeks apart. It's a little bit of a PSA style definition there. Their primary endpoint of EFS was longer with PAXG than Folfurinox by 5.8 months One year. Event-free survival was up 16% and the hazard ratio was 0.64 and it was highly significant and the hazard ratio was 0.64 and it was highly significant. The secondary endpoint of overall survival was an improvement from 26 months with Folfiridops, which is doing pretty well for this group of PDAC resectable borderline, up to 37 months with PAX-G.

Kate Clarke:

Pax with an A Now that was not significant but the hazard ratio was 0.7 and there was 80% crossover to the alternative regime. Grade 3 or 4 TOX was increased with PAX-G but only because of neutropenia and the infection rates of febrile neutropenia were the same and the neuropathy rates were much lower with PAX-G than they were with falfurinox. So actually I'm going to call it. I reckon this is a regime that has actually got some legs. It's better than gemobrexane on its own and it looks to have the edge in terms of event-free survival on falferinox and actually falferinox is tough stuff. So I reckon we need to give this regime a second look. What do you reckon?

Christopher Jackson:

Kate, yeah, look, I'm gutted because I hate being wrong and I can't stand it. Now I could argue about the original version of this regimen with the anthracycline. I can get all high and mighty about anthracyclines and GI cancers, but no, this is a good regimen, you know. It's lower doses. It seems to be tolerable. I agree, the reporting of blood tests that don't affect patients pisses me off. The only thing in New Zealand is access to the NAB, but otherwise, you know, I think we could play with this. When you meet somebody with pancreatic cancer, a small minority of them are actually genuinely well enough for Folfurinox and to be able to enjoy a reasonable quality of life alongside it. So having an alternative regimen that's more effective, that's easier to deliver or it feels easier to deliver, feels like something that I'd like access to. So, yeah, I'm going to have to swallow some very humble pie and say maybe I should be thinking about this.

Craig Underhill:

Why don't you set up an AGITG phase two, Chris, and collect some data perspective? There's always a learning curve, isn't there, when people aren't familiar with yeah, I think so dosing and managing side effects. But anyway, interesting paper, but let's move on to some. You're going to tell us about some of the skin stuff.

Kate Clarke:

Yeah, I will do. I'll move on to skin cancer Now. This is simiplimab. Simiplimab.

Kate Clarke:

Simiplimab, another anti-PD-1 monoclonal antibody of the pembrolizumab-divolumab family and this is in squamous cell carcinoma. So this is in completely resected squamous cell carcinoma with some high-risk features. So that might be perineural invasion, might be lymph node involvement, it might be extra nodal extension or it might be a node over two centimetres. So early stage disease, completely resected. And what they found was an improvement in DFS at 24 months from 64% up to 87%, which is again a stunning 23% improvement in disease-free survival. There was a reduction in local, regional recurrence of 80% and distant recurrence was down by 65%. Os at two years was similar between the two arms and crossover was permitted.

Kate Clarke:

It's a randomized phase three study. I think this has to be looked at in conjunction with the neoadjuvant simplumab study. That was a slightly higher risk patient population, often borderline, resectable which with a lot of T4 tumors or T3s it could have disfiguring surgery, and it had a PCR rate of 51%. So I think there's going to be a lot of debate as to whether neoadjuvant simplumab for four doses versus adjuvant simipramab for a year is going to be the standard.

Kate Clarke:

The other thing I think which is important about the adjuvant simipramab study as well is that the control arm did pretty well. 64% of the control arm with high risk still had no recurrence and that means that two thirds of the patients are over-treated with immune checkpoint inhibitors who do not need it Now. It is a good gain 23% and yes, there is activity of salvage checkpoint inhibitors in metastatic disease, but I very much doubt it will be a 23% plus in DFS for late treatment. So I think that's an important study. I think that it will become an option for people who've had resection in high-risk features, but you'd need to advise the patients that two-thirds of them are going to be overtreated.

Craig Underhill:

Yeah, sure it is a jump forward, though, chris. I think this is one of the first positive studies in this field for a long, long time. We actually recruited patients to this at our centre. It's actually hard to recruit them because the high-risk features are really quite low proportion of patients, and so it just raises my mind about being able to transfer the transferability of this study to, more broadly. You know, cutaneous SCC. Yes, you do have to worry about over-treating people, but you know single agent IO is much different to the epinevo combinations with toxicity, but nevertheless, you're still going to render some people having life-changing toxicity, such as diabetes or rheumatoid arthritis or other things.

Kate Clarke:

Yeah, I really agree with that, craig. I think, though, that the extent of EFS is better than, say, stage 2 melanoma is, for example, or stage 3A melanoma, so the extent of benefit is certainly higher than in that situation, and we know that in melanoma you can salvage people, whereas I don't think you can in this disease to the same extent. So I think it is an option, and if I had a high-risk patient, I'd certainly consider it and discuss it with them, although without our OS, at this stage I think it's hard to say it's a mandatory treatment.

Craig Underhill:

Yep, and these are people who have horrible disease. They've failed multiple surgeries, failed radiation, they've got tumors burrowing into their face or their skull. It's a pretty horrible subgroup of people with nasty SCC. So I'm going to go through some lung cancer stuff. There's a couple in small cell lung cancer. So our first one is abstract 8006 called IM4. And this was looking at lorbinectin plus cetezolizumab as a first-line maintenance therapy for patients with extensive stage small cell lung cancer. So again, this was at a lot of press. But when you go through some details in the data we saw a PFS increase from 2.1 to 5.4 months and median overall survival going from 10.6 to 13.2. So this is again an expensive combination novel chemotherapy drug plus IO in patients that are going to fail treatment eventually and die unfortunately of their extensive disease going to fail treatment eventually and die unfortunately of an extensive disease. So I'm not sure there's going to be too many regulators that will jump on board that, but we'll wait and see. People need to be, I think, aware of that data.

Craig Underhill:

The next one in small cell lung cancer also, rather than maintenance, this was a second-line treatment. So the first study, the Lurbidectin and Teaser study, was people who were still in remission after treatment with standard chemotherapy and then went on to maintenance. This second study, late-breaking abstract 8008, second-line Tarlatamab showed an improvement in survival over chemotherapy of people who'd failed progressed through chemo. So this is a biospecific antibody, so this had a clear difference in median overall survival was 8.3 months versus 13.6. So here we are. Overall survival is an endpoint in a study, interestingly.

Craig Underhill:

But there was significant toxicity with this drug being a biospecific antibody. And so again we're talking about people who have advanced disease, who are going to live longer but still ultimately succumb to the disease, and so there's still a different spectrum of side effects that people need to be able to learn to manage to, I think, not have a detrimental impact on people's quality of life during this treatment. But that received a lot of publicity, concurrent publication again, and was being trumpeted as a new standard of care over chemotherapy for people with relapsed small cell lung cancer. And so again in the context of history of treating small cell lung cancer, and so again that's in the context of history of treating small cell lung cancer. This is quite a significant landmark study. No comments from the press gallery.

Christopher Jackson:

No, no, keep on chugging, keep on chugging.

Craig Underhill:

All right. So we switch now to EGFR, mutated non-small cell lung cancer. This is about 30 to 40% of lung cancers have EGFR mutations and the standard of care has become osimertinib. This was a study comparing chemo. So often people fail osimertinib they go into second line EGFR TKIs or can have cisplatin-based chemotherapy. This was a study comparing cisplatin-based chemotherapy with patrotumumab-deroxicin. So another ADC, this time targeted against HER3. And this had a small benefit in progression-free survival compared to platinum-based chemotherapy, nevertheless being trumpeted as a potentially new drug that will be subjected to further studies in this group of patients. So, rather than people needing to go back onto chemotherapy, there may be some other targeted therapies. But again, these drugs have different spectrum of side effects and in fact the grade three events in this drug, in particular hematological and interstitial lung disease, was higher than the patients receiving chemotherapy. But again, a drug I think that we'll hear more about in the lung cancer space.

Kate Clarke:

Undoubtedly. I think I always get slight antibodies and it may be a bit unreasonable, but it's a bee in my bonnet when it's referred to as patients have failed two lines of therapy. I think it's like those lines of therapy have failed the patient rather than the other way around.

Craig Underhill:

Yeah, there was also some further updates from Checkmate 816, giving three cycles of neoadjuvant, novolumab and chemotherapy in patients with resectable non-small cell lung cancer. So giving them some treatment upfront and that had. It's interesting, this got a presentation of median overall survival. The hazard ratio is 0.72, with a range of 0.52 to 0.998 with a p-value 0.048. And this is on pre-specified time points. I think it was valid. But response rates, receptability, progression-free survival better. Now We've got some data that maybe there is a small benefit in overall survival as well. All right, now some other things GI, some further follow-up. Abstract 4505, which is checkmate 2.14, final results confirming a survival advantage longer durable responses for NIVA, ipi versus sinitinib in metastatic renal cell carcinoma. So this is a fairly complicated field. So for a long time we were treating people with TKIs and now we have IPI, niva and we also have combinations of TKIs and single agent IO and there's some stratification and choice after discussion with the patient, some restrictions on drug listings according to poor risk patients or intermediate risk patients. But this was the final results from this landmark study which showed a clear survival advantage for ipinivo over sinitinib, which is now sort of parked. I think it's used much now as a single agent drug and with very durable responses. It's hard to describe the curves on an audio podcast but there's quite a substantial tail on the curve and suggestion of a plateau with the ipinivo at around. You know, at six years and eight years follow-up about half the patients are still alive. So it's quite substantial numbers of patients compared to about 20% in those who receive sunitinib. So there's obviously in some renal cell cancer patients have slightly progressive disease. So there's always that bit of a tail on the curve but quite clinically meaningful difference when you see those curves. However, in urothelial cancer, bladder cancer, abshack 4, 5, 0, 0, further follow-up showed that ipinivo is really no better than gemcarbo and an interesting discussion. This is almost a historical trial now because we know from last year's ESMO the standard of care if you can afford. It has become the antibody drug conjugate in fortumab, vedotin or EV plus Pembro, and so this study was presented as the final results and that was epinevo versus gemcarbo, which probably wouldn't be repeated now because the gemcarbo would not be considered to be the comparator but nevertheless considered to be the comparator. But nevertheless the 36-month overall survival is 29% versus 19% and at 60 months 23% and 14%. So not quite exercizumab differences perhaps, but similar. So it's interesting now for first-line urelial cancers. You know, chemotherapy is no longer kind of the first thing that we reach to if you have availability to the antibody drug continent. So it's an immunotherapy.

Craig Underhill:

And then in the GU space, another interesting study amplitude, late breaking abstract 5006, late breaking abstracts. Breaking Abstracts seem to be. We've presented a lot of those today. This was a study in prostate cancer called Amplitude. So this is in a population with a big unmet need.

Craig Underhill:

This is prostate cancer hormone refractory. There's many millions of men around the world that would have that disease. And this was comparing a PARP inhibitor plus abiraterone and acetate and prednisolone in patients with homologous repair, gene altered, metastatic carcinogen-sensitive prostate cancer. So these are men either with BRCA mutations or effectively acquired BRCA mutations in the tumor or other pathways of homologous DNA repair. And you can now test tumor samples for that, looking for those HDD or homologous deficiencies. So this was a study, as I said, combining niraparib PARP inhibitor with abiraterone in these patients About one in four men with metastatic carcinogenic prostate cancer have these mutations and showing a small but meaningful advance in the treatment of these men. The norepinephrine does lead to hematological toxicity is often the main issue and they need fatigue and they need some dose reductions. But I think there's going to be again a lot more studies focusing on this subpopulation of men with hormone refractory prostate cancer and the homologous repair mechanism deficiencies.

Kate Clarke:

Craig, what sort of proportion of patients have that?

Craig Underhill:

One in four with metastatic carcinogenic prostate cancer. Show the homologous recombination repair.

Kate Clarke:

One in four. That's quite high. It's a lot higher than I thought it was.

Craig Underhill:

Given the prevalence you know, in Australia I think it's the second most common cancer. We have probably colon cancer number one because males and males and females, and then prostate, and then breast and then lung to begun that need and these are oral drugs.

Kate Clarke:

Yeah, well, that's substantial. The PARP story hasn't been playing out so well in pancreas, cancer really has it, and there's questions about that in ovarian too.

Craig Underhill:

And just a couple of others. To finish off, olanzapine. That's one of our favourite anti-nausea drugs and there was a study using it in radiation therapy and it works, especially people having radiotherapy to the abdomen or pelvis. So that's something to think about. If you're having people, maybe if you're a medical oncologist listening, you have people on concurrent treatment or or for the radoncs listening onlanzapine is an effective drug. This is a low dose. This is not the antipsychotic doses but the low dose antiemetic dose and one other one we should mention.

Craig Underhill:

This is a niche cancer for many of us head and neck squamous cell carcinoma. But late-breaking abject 2. 2 called NEVO, post-op showed a disease-free survival benefit. For people who had standard care surgery and had high-risk features, receiving nivolumab post-op showed disease-free survival benefit. It's too early to talk about overall survival but this may well become a standard of care, I think, in the treatment of head and neck squamous cell carcinoma going forward. So the disease-free interval for people who'd had this sort of people had surgery or chemoerotic therapy disease-free survival of nivolumab plus chemoerotic therapy versus chemoerotic therapy alone at three years was 63% versus 52% disease-free survival. Again, these are people with nasty squamous cell carcinomas, a head and neck so is there anything about P53 there?

Kate Clarke:

Craig?

Craig Underhill:

So that's a great question, professor Jackson. So there's actually a separate study going on answering the same question in the HPV-positive population, because they tend to do better. So it may well be that going forward, the use of IO might be stratified between those two groups.

Kate Clarke:

It's good to see so many abstracts coming through this year which, looking at the adjuvant setting again, right, you know that's where we want to have all of the action isn't it is the cure space and also want to be seeing improved quality of life and length of life in the advanced disease situation this year. My take on ASCO was there weren't quite as many simultaneously reported quality of life data at the same time. Last year or two years ago, they did a couple of simultaneous publication in Recto in particular for quality of life stuff, which I think was good. And we've still got the habit of the trialists thanking the patients and their families, which I think is great to acknowledge that. What I'd like to see as well on one of our group chats, one of the patient advocates was saying why don't they acknowledge the patients are involved in the conception and design of the studies as well, because you know, actually they're key partners in the development of the research programme too. It'd be great to see the patient representatives acknowledged in the terms of the design of it also.

Craig Underhill:

Yeah, I think it's becoming standard of care now in the design that there needs to be consumers included. I'm not sure if that's always done in the commercial space, but certainly in the cooperative groups that is done. I think there needs to be consumers involved in the interpretation, as you say, chris, and so that's where you know throwaway lines like acceptable toxicity.

Kate Clarke:

Yeah need to be challenged.

Craig Underhill:

Eh lines like acceptable toxicity may disappear if you actually have people who have been affected by the toxicity.

Kate Clarke:

Yeah, and I think that including the people affected with cancer or individuals with lived experience and the design is relevant for pharma as well, and if there's anyone who's in pharma who listens to our podcast, I certainly hope there is. I think if your goal is to answer clinically meaningful questions that matter to people with lived experience or patients with cancer, then you've got to include them in the design stage. It's just common sense, and so that's really important to do that. Irrespective of whether it's a cooperative, academic or a commercial study, they should be included.

Craig Underhill:

All right, Well, ASCO done for another year. There's so much data, isn't there? People can still spend quite a lot of time looking back and thinking about that. We've only scratched the surface with some of the sort of main papers or main things that might change practices a whole wealth of information, some great sessions on supportive care, global oncology and there was quite a little bit of chat on Twitter, too, about people mentioned that they thought the education book was particularly good this year, and I think that's probably something people need to think about to learn a bit more about these emerging antibodies. They might be in a particular tumor but might come across to their tumors down the track, but that education book is a source of knowledge as well, and that's available online for ASCO members.

Kate Clarke:

I must say I've never actually read the educational book Craig. I like enjoying the trials, but maybe that's something I should do Exactly.

Christopher Jackson:

The other wee hint is, if you've ever been to the ASCO meeting but you didn't go this year, you can still see the abstracts within the app and it's a much more user-friendly search than the website. So if you've downloaded the ASCO app, you can look at upcoming meetings and past meetings, you can download the abstracts without attending and it's a really user-friendly model. So I think their phone apps are much better than their other apps Just a wee hint for new players, that's great Good tip.

Craig Underhill:

Thanks guys. Thanks, Professor Jackson, Thank you, Dr Clark, for your input and your hard work putting this together. Thank you to Rachel, who is frozen on our screen and may not be able to speak. But thanks, Rachel, as always, for nudging us in the right direction and putting the show together, and please look forward to some feedback and we'll be back soon with a regular episode.

Kate Clarke:

And you enjoy London while you're there. Craig, this is Oncology Journal Club International Edition. Signing off Ka kite. Thanks, craig. This is Oncology Journal Club International.

Rachael Babin:

Edition. Signing off Ka kite. Thanks See ya Ka kite, bye, bye.

Rachael Babin:

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.