The Oncology Podcast

The OJC ASCO 2026 Special Part 2

• The Oncology Podcast • Season 4 • Episode 5

Share episode

Use Left/Right to seek, Home/End to jump to start or end. Hold shift to jump forward or backward.

0:00 | 49:30

Send us Fan Mail

S4E5 The Oncology Journal Club Podcast 


The Oncology Journal Club team returns with Part 2 of its ASCO 2026 coverage, delivering a whirlwind tour through some of the most interesting studies presented across gastrointestinal, breast, lung, genitourinary, gynaecological, skin and haematological cancers.

Craig Underhill, Kate Clarke and Christopher Jackson discuss emerging data on ctDNA-guided treatment strategies, exercise as adjuvant therapy, genomic testing in breast cancer, novel antibody-drug conjugates, immunotherapy advances, de-escalation studies and potential new standards of care. They also explore the growing role of precision medicine, evolving treatment sequencing strategies and the challenges facing the global oncology workforce.

Along the way, expect the usual OJC banter, ASCO bingo, questionable drug pronunciations and a recurring tribute to Qantas pyjamas!

The Oncology Journal Club Podcast is hosted by Professor Craig Underhill, Dr Kate Clarke and Professor Chris Jackson, and proudly produced by The Oncology Network

Visit oncologynetwork.com.au for Show Notes, to send us Voice Notes and more information. And to download your bingo card if you'd like to play along with the team!

Welcome And ASCO Bingo

SPEAKER_01

Hello and welcome to the Oncology Journal Club Podcast, where Oncology papers meet real-world practice. I'm your producer Rachel Babin, and joining me again are Professor Craig Underhill, Dr. Kate Clark, and Professor Christopher Jackson. Together they dive into the research shaping cancer care: the important, the intriguing, and the sometimes controversial. This podcast is proudly produced by the Oncology Network. Head over to OncologyNetwork.com.au for the show notes with links to all of the papers discussed today. Okay, over to you, Craig.

SPEAKER_00

G'day, g'day, g'day. Welcome to episode two of the Oncology Journal Club Podcast Ascow Special or Post Ascot special. G'day, Professor Jackson.

SPEAKER_04

Yold uh, how are you, Craig? Uh did you miss out on being an ESCO this year? Were you sad not to get your quadrus PJs?

SPEAKER_00

I was, yes, very much so. And Kay, how are you doing?

SPEAKER_02

Chris is winning on bingo already. Um very well, thank you. Very well indeed. Finally getting over. It's ridiculous. You're only there for a week. Completely throws you sleep up the yin-yang. But uh, but back again.

unknown

Yeah.

SPEAKER_00

It does. So we're gonna be playing Asco Oncology Bingo. Or Rachel's gonna be playing bingo. Get out your bingo card, Rachel. And there's some bonus points. Every time Christopher mentions that he presented at Esco, there's a bonus point. Anytime that I mentioned quantus pajamas or missing out or mispronounce of a cracker name, you can get a bonus point. And for Kate, it's anytime she mentions sexual dysfunction, menopause or vaginas, we get a bonus.

SPEAKER_07

So what's the thing that could be scored out of? Is it gonna be scored out of like a hundred? Because Kate's gonna mention those things like 30 times each.

SPEAKER_02

Yeah, yeah.

SPEAKER_00

All right. So this will be a bit of a cook's tour through the uh conference centre with some quick bites, various tumors and uh new things. Some of them practice changing, some practice affirming, or some just interesting uh new data. Just to recap with episode one for those who haven't listened yet, and we've had sort of a pretty uh impressive uh uptake or downloads uh in the first uh 36 hours since that was released. We're very pleased and thankful for all the people who have done that and listened. We uh basically went through the plenary session. There were some fantastic uh papers presented, a Proteus paper, which is uh using uh perioperative apollutamide in uh men having radical prostatectomy, abemacyclib in patients with advanced dedifferentiated liposarcoma that Kate talked about, advanced stelpus catinin in stage one B, three A ret fusion positive, non-smell cell lung cancer, the libretto trial, harmony six, adding ivonoscomab uh to chemotherapy and tisilusimab in uh squamous or carcinoma and the one that got all of the attention uh Rasolute 302 Dirac on Rasib for metastatic pancreatic and no carcinoma. So it was a pretty impressive plenary session. So, but let's get into episode two. Professor

Colorectal Updates And ctDNA Limits

SPEAKER_00

Jackson, you're gonna tell us uh about some GI, no doubt, and some melanoma papers as well.

SPEAKER_07

Yeah, thanks, Craig. I'll I'll start by covering off the colorectal session. I think uh the colorectal stuff this year, not heaps of stuff, was uh practice changing, but it's uh good just to go over what we had. We'll start off with the colorectal LBA3500, which was circulating tumour DNA in stage two colorectal cancer, which used an academic tumour-informed circulating tumour DNA essay. So it was cheaper than the standard commercial ones. Um and they randomized people who were CT DNA positive to capox or ketamine or observation. If they were CT DNA, they were um randomized to observation or off-study. So it was attempting to move from simply being prognostic to being predictive. The uh very sobering finding on this was only 4% of patients um were CT DNA positive. So it's actually pretty hard to use the circulating tumour DNA positivity as a strategy for stratifying who should get chemo and who shouldn't in stage two colorectal cancer. The conclusions of the study were that CT DNA remains strongly predictive, but not enough data regarding its predictive power. Uh, and it may just be because our tools and adjuvant are blunt. You know, capsodamine capox is a pretty um blunt tool, no real escalation or intensification strategies there. And I also wanted to do a quick shout out to Margaret Lee and Genny T from um Nelwyn, who had a post-up in the colorectal session on um peritoneal uh tumor DNA as a predictor for peritoneal recurrence. So good on them for uh bridging the new divide there. Uh and Margaret was presenting a poster there, had a lot of interest. Uh LBA 3502 was a, I love this one, a Chinese abstract. Why do people even have to say what country comes from if it comes from uh East Asia, right? Why do they do that? Anyway, this was a really great observational cohort study of deficient mismatropic colorectal cancer, uh, patients who were treated with immune therapy. In this situation, people were either treated for two years or to CR plus two cycles. Um observational duration study. Um, and what they found was that numerically, uh, those who were treated to CR plus a couple of cycles, only one or two of those patients actually relapsed and they were both salvageable. And there was no clear survival gain for those who continued for up to two years of uh maintenance I.O. And the grade three TOX was lower uh with the CR plus two strategy compared to the two years uh maintenance with grade three TOX rates of 3% versus 11%, which of course is subject to ascertainment bias. So observational study, hypothesis generating, et cetera, et cetera. But, you know, it's pretty daft that we use this very arbitrary two-year duration of I.O., isn't it, for most of these studies? Uh, and having some kind of duration, uh, which is rational, uh, at least, seems like a great way to go. And this might encourage people to do a genuine randomized duration study. We'd love to see that happening. Well done to the investigators for reporting that uh abstract and getting that into the oral session. A 3503 was the breakwater fulfuri uh study. So just to recap, breakwater um is for BRAF mutants metastatic colorectal cancer uh and was a randomized study between Dellers-Joyce chemotherapy and fulfox with encocetux or fulfuri with encocetux. Now, they had a safety lead-in for fulfuri because there's a theoretical interaction between Iranitacan and Encorefinip, and so they thought that might cause problems. So the safety lead-in found there wasn't a major safety signal and then went on. Now, we've all had the full fox encocetux versus chemo arm. We know that's been reported before, uh, and we know that's positive for PFS uh and OS. So doubling of both PFS and OS compared to dealers' choice chemo. And this was comparing fulfurry EC to chemotherapy. Now, the highlights of this uh were that we saw a medium PFS of 15.2 months with fulfuri EC with no new safety signals. Thank you, no new safety signals. And actually, if you compare that to the fulfox in the study, it was actually only a medium PFS of 12.8 months. Of course, with fulfox NCO Saturgs, you drop the auxiliplatinum and they start to give a bit of neurotox, but with fulfuri, you're not dropping the doublet. So you're continuing on for a bit longer. So maybe that doublet with fulfuri might even turn out to be a better strategy in the longer run. This is not a clean comparison of fulfox or fulfuri backbone with encocetux. That's not what the study uh was reporting at this stage, but it is showing that folfuri with encocetux is a perfectly acceptable choice in that BRAF mutant population. I think that's practice affirming. Many people are already using fulfuri encocetics or equivalent, and that's because many of our patients have already relapsed adjuvantly, and so are not able or are not able to have oxidoplatin for other reasons. So I think this is reassuring. LBA 3504 was a second-line BRAF mutant population. It was looking at encocetux plus minus NEVO because a pre previous singular phase two study looked at whether or not NEVO NCOCTAX might have some activity in people who previously been treated with BRAF mutants, MSS, micro satellite stable, not DMMR, micro satellite stable cororectal cancer. And the long or the short of it was that it was a very negative study. So please don't go giving uh your BRAF mutant patients who've relapsed NCO satux with NEVO. Don't do that outside of a clinical trial. Very important not to follow that strategy at this particular point in time on the base of evidence we've got. A 3505 was a HER2 positive population. Looking at an antibody drug conjugate of Transtuzimab Resitican, so not Duroxtacan, but resitican, which is allegedly better because a different company makes it. And that was um compared with standard care chemotherapy. A little bit of a growth in PFS plus 2.5 months. Hazard ratio was pretty good at 0.33. I'd call that a signal rather than a slam dunk. PFS gain of plus uh 2.5 months is only really an ESMO, two or three MCBS scores, not very high, uh, but it's a signal that targeting her two with drug antibody conjugates may still be a good strategy. And the last decent one out of the colorectal oral session was the cost-effectiveness study from the challenge exercise study. People remember that challenge is the most important study, never to get an ASCO plenary of adjuvant exercise and fully resected stage two and three colon cancer following on from adjuvant chemotherapy of structured exercise versus usual care. This was the cost-effectiveness study. Uh, and what I love about the study is it showed it actually saved money uh compared to usual care. And that was because, of course, it stopped people relapsing and therefore fundling the structured exercise program actually saves their health system money. One of the key points they mentioned, though, was that you have to really pay the exercise people uh per hour because if you pay them on salary, it might not deliver those savings. So it's important still how you structure uh the funding for it. That's been published in JCO and is available to look at. So post it to your local HTA uh or your local hospital administrator and say, look, I've found a way to save money. Next time you're told to save money, go, I've got a way. Set up an exercise program, it'll save you money and see if they jump at it. They were the key highlights from the uh correctal session.

SPEAKER_02

I I just wanted to stress that the cost effectiveness, when you save money, it's called a dominant strategy. And I just think that's brilliant on the health economy nerds to come up with that concept. So so it's a dominant strategy, which means that we should all be doing it.

SPEAKER_00

Dominator. And CJ, how did they save money? Was it both saving readmissions or relapses?

SPEAKER_07

And yeah, saving relapses, Craig. So, I mean, if you're saving uh relapses and you're saving the interventions that you need to do when those people relapse, uh and so it was a really good uh cost-effectiveness study. Very detailed. They did all these things called bootstrapping and stuff, which I don't really understand. But I do so like a study that confirms my biases. Yeah, fantastic. That was one of them.

SPEAKER_00

When when the Challenge study was released, I think it was last year, I remember there was a mention that there was more papers to come, including a cost-effectiveness. So that's um great to know that it was a positive, fantastic, because that that's often touted as a barrier, it's an additional cost of having to set up exercise programs.

SPEAKER_07

Yeah. And uh one of the things that I mentioned in my ESCO session that I talked at uh was that our most of our health systems don't actually have very good pathways to reimbursement for these non-drug-based uh interventions. And you'd have to think that if um age of an exercise was a drug, so we call it exercise a mab, um, that it would be funded by most health systems at the moment because you've got very rapid pathways for evaluation and reimbursement. And most of our systems, like the PBAC or FAMAC in New Zealand, we just don't have those systems for funding health systems interventions, but a clearly uh cost-effective intervention that reduces overall deaths by as much as oxalyplatinin more than her septin and HER2 positive breast cancer should be a slam dunk for most health systems, but it's really still not funded uh routinely in most health systems anywhere.

SPEAKER_02

But it is truly a a whole of health system benefit. And the tricky part is which part of the health system is going to front up with the cash first, and I suspect there will be arguing for ages about that, even though we acknowledge the benefit.

SPEAKER_00

I'm sorry I missed your presentation at Asco, Christopher, but I did um enjoy watching some of the sessions online in my conscious pajamas. Would you like to go next? Next.

Breast Cancer Testing To Skip Chemo

SPEAKER_00

Hopefully, I think we're a bit of breast cancer. I am some pretty exciting abstracts in breast cancer, I thought.

SPEAKER_02

Yeah, look, I think the most exciting, though uh I suspect many drug companies won't agree with me, the most exciting is Optima, which did recruit in both New Zealand and Australia. Uh it was uh through a I can never get the acronym right, A, B, C, D, C, G, lots of letters. Uh Rob Stein's group. I worked with Rob in 2008, so this is uh something that has taken a long time to get uh here out of UCLA. And the concept was looking at a much higher risk group of women in the adjuvant setting. Uh so they did include men, but it was by by and large, uh, by and large, so people with breast cancer in the adjuvant setting, much higher risk. Your oncologist working in mostly Britain and Australasia had to be comfortable with you needing chemotherapy. And then they were split into a control arm and a test-directed arm. Those people who were in the control arm were mandated to have chemo, mostly dose attacks of cyclophosmide, followed by endocrine therapy. Premenopause or women had to have ovarian function suppression as standard. Then in the test-directed arm, they had prosigna, which is the more affordable of the commonly used uh gene assays. And then to be called high score, you had to have a score of more than 60. That only applied to a third of the women who were in the group. And I'll come back to the group inclusion in a second. Um, and then if you had a low score, you just got endocrine therapy, including our ovarian function suppression if you were pre-menopausal. Otherwise, uh you were uh if you're high score, you got chemoendocrine. Trial had some really nifty, relatively modern things included in it, uh, in that the non-inferiority margin was decided by a community, including patient and patient advocates, which I think is really important. So they were comfortable with a 3% absolute non-inferiority margin for um invasive breast cancer-free survival. And the inclusion, the women, only 10% were node negative. And included women are over 40. So that's quite young women. Significant number, 20% had four to nine lymph nodes involved. So this is a what we would consider a high risk legend. Is it because of 70% of people had a low risk score? Associate Professor Steid was quite uh clear that they tried in the uh start, they used ovputype DX as well, but onputype DX gave significantly more women high risk uh scores. The non-inferiority margin was not breached. There is a uh numerical difference in the groups between uh either test assigned or giving everybody chemoendophrine of uh about 1% on all endpoints. So invasive risk, gets a free survival, distant recurrence free survival, confidence intervals clearly crossing one and all of those things. And that included they've breaking them up by menopausal status, they're broken up by A's, they've broken them up by traditional stage. So I think this is a great strategy. So health systems can avoid uh spending thousands on uh chemotherapy and the admissions thereof, and women can avoid 12 weeks of what is significant uh downside uh to their lives. So this is very awesome. So I was very excited by that. Lovely to see Rob looking so well. Yeah, it was good.

SPEAKER_00

Can I question on that one, Kate? Of course you can. The optima test was so how many of those women considered high risk were found to be low risk on the optimum tests?

SPEAKER_02

So 70% of the women who had clinically clinically high risk disease.

SPEAKER_00

Seven zero. It's quite a bit.

SPEAKER_02

Seven zero. It is quite high.

SPEAKER_00

And did you say they all had the oncotype DX as well? And there was no discord between the two?

SPEAKER_02

No, not all of them. In their pilot phase, they get all women had both, uh, and there was significant discordance. And oncotype DX put more women into a high-risk group.

SPEAKER_03

Yeah.

SPEAKER_02

The published data is about the ProSigna. And even with the ProSigna putting more women in the low risk group, the difference is still insignificant between a chemo endocrine strategy and a risk-adaptive strategy.

SPEAKER_00

Great. And this was survival data, or this is relapse-free survival.

SPEAKER_02

We're only at five years. So we've got invasive breast cancer-free survival and distant recurrence-free interval. The feeling is, and it has been what's called Ponderex and Taylor X alreded five year as well, because that's apparent, that is the feeling. That's the the chemo-prevented recurrences. The late recurrences are hormone-related recurrences. Okay. Pretty exciting. So I know everybody's furiously writing to their funders to say if you don't have access to these, uh, you probably should.

SPEAKER_00

Um and just for people who don't know, don't regress the oncotype DX is kind of the standard, which is thousands of dollars for the testing. This is hundreds of dollars. Is that correct?

SPEAKER_02

No, sadly, this is still thousands of dollars. It's it's fewer, fewer thousands of dollars, but it's still thousands of dollars. Okay. Uh but uh cost saved. Uh then I wanted to very briefly talk about um uh a trial that I think was mostly done looking for the safety, but has come out with an interesting uh uh hypothesis. So uh American College of Radiology took a crazy number of women who'd had any kind of breast imaging over uh several years and looked at their GLP1 use and looked at their incidence of breast cancer. Understanding this is a retrospective observational study, they've done that propensity match business, which I would never understand. But there is a 30% reduction in breast cancer incidence. So GLP1 agonists are probably safe in terms of breast cancer risk. Are they uh protective? That's for a future study. But I'm I'm fascinated by that. There were several GLP1 agonist uh studies in other disease types, too, looking at lower metastasis rates and all sorts of other interesting stuff.

SPEAKER_07

I think that's a really important study because I think that people think that GLIP 1, when they reduce the obesity rates, will actually naturally or follow that you'll reduce the cancer rates. But there's been some conflicting data in pancreas, for example, um, whereby some studies have shown a slight excess risk of um pancreas cancer in GLIP 1 users, uh, whereas others have not found that. So I think it is important to continue to collect the data and to continue to look at that and keep an open mind about which way the relationship's going to go.

SPEAKER_00

It being an endocrine-driven cancer, you would think that kind of looks biologically plausible in breast cancer, right?

SPEAKER_07

Uh possibly. But also I think the other issue is that it's it's not a straightforward relationship. Sure, it's obesity, but also there's a degree of sarcopenia that the glip ones can cause as well. So you can lose muscle as well as fat. And so I think there's a complex interplay there between the body composition stuff. So I don't necessarily think it it's a slam dunk that it's going to happen. Of course, it seems plausible and likely, but I don't think you should just assume it. Uh, and that's why the data should be collected. I don't think it's enough of a concern to say you shouldn't market it until you've got the data over 10 years or 20 years or whatever. But I do think it's important to continue to monitor and keep an open mind about what the possible direction of the risk is.

SPEAKER_02

Yep. So the the other breast cancer one I wanted to talk about really quickly uh was denosimab dose density that came out of the Swiss Cancer Institute. So many of us who treat breast cancer, uh, we use uh bisphosphonates uh or denosimab, a slightly different mechanism, to uh prevent skeletal-related uh events, uh, particularly in estrogen sensitive breast cancer, where women may have very many bone metastases. And the standard dose for a long time has been Q4 weekly for a long time. Some years ago, a group of investigators who I have forgotten about suggested that you could, after a year, drop the dose uh of cylindronic acid to every three months, and that didn't seem to take away the benefit. Similarly, denosimad, you give a run-in of four weekly for the first 16 weeks, and then thereafter three months compared with continuing on Q4 weekly, you have no loss in the control of skeletal endpoints, no difference in overall survival. Uh, but more importantly, fewer hypocalcemic episodes, fewer ONJ or tooth infections, so ONJ being osteonecrosis of the jaw, and significant cost and time savings. So another very sensible trial coming out. I think clinicians thinking sensibly about what we can stop doing to make room for the things that we should be doing.

SPEAKER_00

So that's quite useful. It's always good to see symbosis de-escalation trials. Do you have anything else to tell us, Kate?

SPEAKER_02

I have one, maybe two other uh like interesting things.

New Pathway Targets Beyond KRAS

SPEAKER_02

So we all got very, very excited, completely appropriately, about uh Daxon Directson Raster, but I was gonna wrong. It's got two but these syllables in it. Anyway, the brand name will be something like PDAC off or something, and we'll all be like, yay, yeah, you know, cure them all. But there's other really cool new sexy ways of uh targeting the K-Ros pathway that are coming. And cyclic mech inhibitors are one of the ones that I think is really exciting. So the drug here, and I've written it down so I can sell it, is at a couple of giggles it.

SPEAKER_00

You can try.

SPEAKER_02

Hours, it's got a very short half-life. So that turns off your downstream signaling, but doesn't allow for resistance to develop as fast, but also allows your normal cells to keep doing their normal things, which I think is quite awesome. Convenient side effect uh of weight gain, which also in a pancreatic cancer population is awesome. So they gave this drug alongside a modified NAPACL gem cytoveme. So every every two weeks rather than three weeks on one week off. And the difference, the um progression-free survival uh in first time was 8.3 months, and the overall survival is 17.3 months, uh which compares favorably with historic controls. So I'm very excited. There is uh a global randomized phase three on the way called Map Keeper. So they obviously understand their name is too hard to pronounce. So I'm very excited about that.

SPEAKER_07

Fantastic. Okay, were there any um abstracts that resulted in symptom improvement or improved quality of life? Or I'm trying not to say it, any possible hormonal benefits in patients out of any of the studies that you were discussed?

SPEAKER_02

Uh no, you know, I wasn't actually focused very much on sexual function as Esco. It might have been the card the I was cute.

SPEAKER_07

And I think uh I was sitting next to Kate in a couple of sessions while Craig was at home in his quantus PJs, and Kate was complaining about the uh temperature in Hall D, which those have been to Esco in recent years will remember is a frequent problem, and Kate said Where's a hot flush when you need one?

SPEAKER_02

I well did, honestly. I could have hopped out an eye with the nipples that I had on me.

SPEAKER_05

You're gonna really do um wonders for our our R ratings on this particular podcast. Remember, why has the Oncologist Journal Club got an R rating for a scientific review?

SPEAKER_02

I did have one more. I found this really interesting. This is another unpronounceable drug. Onvancertib plus standard of care kinotherapy plus better cismad, in first line, rhaz-mutative medicinic colorectal cancer. Onvencertib is a highly selective oral small molecule inhibitor of PLK1. So it is involved in mitotic progression, DNA repair, and tumor cell adaptation to hypoxia. So if you block that, you make cells uniquely sensitive to arinoticin, but not uniquely sensitive to oscillophatin. And so what they did was they looked at fulfill onvencertinib and bevisismeb versus bulfurio bevisismeb and fulfox onvencertinibesmeb versus fulfox bevisismeb. There's no difference in the oscillophlatin arm. It's exactly the same. In the arinitican arm, there is a significant difference. And obviously, this is early, this is phase two, significantly more responses. Those waterfold plots look really sexy, including one, two, three, four, five, so that's probably what 30% CR rate, which is pretty, you know, in metacylic chloride can say you don't see that a lot. Professional resurvival not reached yet. But overall response rate's 72% versus 40%. So I'm hanging out for some of this more synergy and thinking. So that's an on-vancertib.

SPEAKER_00

Yes, but was the toxicity manageable? If it caused hypoxia, what happens? Your toes fall off, or what what was the toxicity?

SPEAKER_02

This is the problem with those five-minute abstracts, is we won't know until that gets published properly.

SPEAKER_07

Okay. So this is a polo-like kinase one inhibitor, PLK1, rather than a HIF. Yeah. Because New Zealand did a bunch of HIF uh alpha studies for a while too, but unfortunately that didn't really go anywhere.

SPEAKER_02

So I think the interesting thing here is that although it's not supposed to work on salad patient hypoxia, the real benefit seems to be in its synergism with aren't T can. So the aren't goes in and blasts the DNA, yeah, so toFISOMRAS inhibitors. Uh, and then this comes in the way and goes, uh-uh, don't fix yourself, please. So it's it's it's so you end up with that that lovely uh illogical term of synthetic orthodoxy. It can't fix itself.

SPEAKER_07

Which is just a full fold synchronicity, right? And you get the DNA crosslink or DNA adapter thing, the auxiliary platinum, the 5v, which are supposed to stop the DNA repeat. Same thing. Uh it's working an um additional uh pathway there.

SPEAKER_06

Cool. Um this is all up inhibitors, Cape. Yeah, biology that you need to know.

SPEAKER_02

Yeah.

SPEAKER_00

Sounds pretty clever though to work out that mechanism that it synergized with the fulfuric. All right. So I've got a few to do. Back

Lung Cancer Advances And Crossover Ethics

SPEAKER_00

to lung cancer. So this was late breaking abstract 8500, the Wukong 28 trial. First line Sunversertanib showing superior efficacy over chemo alone in advanced non-small cell lung cancer with EGFR exon 20 insertions. So there's been an absence of uh effective therapies for these type of uh lung cancers with the uh exon 20 insertion mutation, with fewer effective um options compared to the more common exon 19 deletions or the L858R. And so this was touted as potentially a new standard by the discussion for this uh um rare like cancer. It's an oral treatment. So this was a single agent versus combo chemo. 90% of the patients crossed over. So Chris, the last episode thought that wasn't a great thing to do in the first study of the drug. So despite that crossover, the median progression free survival uh was significantly longer, 10.3 versus seven months, 59% versus 31% response rate. Uh median duration response 11.2 versus 7.1 months. Overall survival immature, there was no quality of life data. Um, and of note there was sing there was a uh higher rate of diarrhoea from this agent. But interesting data, and given the absence of uh effective therapy other than chemo, it would be interesting to see where that uh goes in the marketplace.

SPEAKER_07

Craig, can I just um jump in there and say that thank you for raising the crossover issue. There's a a very good review um on uh the ethics of crossover, which is actually written by Vanet Brasartin, but there's a a 2014 um review article on the ethics of crossover trials, either mandatory or uh we crossover should be with help. It's worth a read, actually.

SPEAKER_00

Thanks, Chris, for highlighting that. So we'll put that in the episode notes, and we'll also maybe we'll put it on our resource, new resource tab on the website, Rachel, so people can find that in the future as well. So another molecule touted as a possible new standard uh in lung cancer. This interesting study. This is optotrope lung O5. So this is uh ADC, the Sacitusimab tyramoptican, given with Pembroluzimab. Uh in PDL1 positive advanced non-small cell lung cancer. So in the past, we've had just single agent Pembroke as an option. This is adding the ADC to it. First phase three study doing that, or first phase three study reported, medium progression-free survival not reached versus 5.7 months, with a hazard ratio of 0.35, so substantial reduction in the risk of relapse. And the one-year progression-free survival 62% versus 29%. There were no new safety signals, but the toxic extra toxicity of adding the sassituzimab TROM at TCAN to Pembroke, you get all the usual side effects of the IO, but there's an additional grade three neutropenia, anemia, stomatitis. Now switching track to G U, we had some follow-up data. Abstract

Urothelial De-escalation And QoL Focus

SPEAKER_00

4507, which is M4Mab for dotin plus Pembro versus chemo. So we've talked about that in the past. I think it was presented at ISMO last year or the year before, or maybe ASCO last year, showing survival advantage with this non-chemotherapy containing regimen for patients with locally advanced or metastatic urethelial cancers. So this is a three and a half year um follow-up. So patients in this study had to be PD1 naive, ECOG2 or less. So they did throw in the ECOG2s. Often these studies have zero or one patients. The chemo was six cycles of standard gem uh gem cytomand and a platinum. Um the M4Mab for dotin was given until progression, so quite a lot of drugs. So that's relevant because I'll get to the toxicity in a set. So three and a half year follow-up data showed so overall survival 33.6 months versus 15.9 months, so it has a ratio of 0.5. So basically doubling the benefit, you get the usual side effects of the Pembro's with all the itises. But interestingly, in the patients receiving the M4Mab for dotin, they have accumulative peripheral neuropathy. Grade three is uncommon, but close to a 90% rate of sensory neuropathy at two years. Overall, the grade three toxicity is less in the EV arm compared to Pembroke. And, you know, this is a study in people with local events of disease or metastatic disease. So at three and a half years, we still haven't seen quality of life data presented in this group, um, which will, I think, help uh in the decision-making process. And following on from that, because the so far the infortramab perdotion uh is only available in US and Italy. So other countries have not listed this, including the rest of the EU, spite of the Italian listing. So this was a study that's relevant probably in other jurisdictions, and also an option where people have relapsed after the infortramab. This was a study called Discus giving avalumab maintenance post-chemo for locally advanced or or metastatic urethelial cancer. So this was a de-escalation study, three cycles versus six cycles of chemo. And there was an identical uh overall survival. So it looks like three cycles of chemo is enough, and then you give the 12 months of the single agent um PD1 inhibitor. And they reported quality of life as a major endpoint. And Chris has just fallen off his chair.

SPEAKER_07

Those investigators are doing that. That's awesome.

SPEAKER_00

Yeah, and so interestingly, the biggest deterioration in quality of life was with the six cycles of cisplatin. You could probably predict that. Less so in the patients getting carboplatin. The highest grade three treatment-related adverse event was in the six cycles of the carboarm, mostly related to hemological toxicity, which makes sense. But so there was a trend in favour of better overall survival with cisplatin, but not statistically significant. So really identical overall survival of about 80 months, regardless of whether patients got three or six cycles of chemo and whether it was cisplatin or carboplatin-based. So this is a really pragmatic trial, I think, for most of the world, that doesn't have access to the new agents.

SPEAKER_07

I mean, that's great for a number of reasons, Craig. You know, a duration study with de-escalation as a strategy. Maybe that's cost saving as well as time toxicity saving and quality of life as a major endpoint. I think there's a lot to like about that.

SPEAKER_00

Yeah. Last one in neurological cancers, abstract 5505, phase two AraColb trial, enzyleutamide versus derolutamide. So we've known for a long time enzyutamide crosses the blood-brain barrier and there's been concerns about cognitive impairment. So this was an investigator-initiated study comparing enzyleutamide versus derulutamide. And the enzyutamide patients did, in fact, have lower cognitive scores. So it's proven the point there is a difference clinically between these two drugs. So I suspect that enzulutamide usage will be on the decline in the jurisdictions that have access to derolutamide as well. Changing gear, and we're gonna mangle this drug for sure, abstract 5515. This was a study in ovarian cancer and endometrial cancer, the blue star study. This is a B7H4-directed toPa1 inhibitor called puxatog, samura T can. That gets the prize for the hardest ever saying molecule, I think. So this was a phase one, two study, active mu agent, response rates of 47% in ovarian cancer and 24% in endometriov cancer. I want to mention too, we don't often cover a lot of hematology, but uh this may be the first study in decades to beat the current standard for patients with high risk diffuselage B cell lymphoma or high grade B cell lymphomas of adding a new drug called Tafacetamab plus lenolidamide to RCOP. So for many, many years, RCOP's been the standard. This TAFACTAMAB is an anti-C19 monoclonal antibody, which is found on the surface of B cells. So the overall survival data is immature, but at 32 months, there was a 25% reduction in the risk of progression or death versus RCOP. The final analysis for overall survival will be at the five-year mark, so two and a half years in. There is a slightly higher grade three toxicity, 86 versus 76 uh percent, which we, you know, in hematology studies, that's not unusual. But the ability to deliver the standard RCOP wasn't compromised by adding in the extra monoclonal antibody. So again, the discussant thought this was a new standard. It was concurrently published in the Lancet. So the benefit was across uh subtypes of different types of uh high-grade um lymphoma.

SPEAKER_07

So can it be a new standard for uh medical oncology if it's not published in the Union Journal of Medicine? Craig?

SPEAKER_00

I don't know to ask a hematologist whether Lancet was okay or not.

SPEAKER_07

I think what's interesting about look, it's been many years since I've treated lymphoma. I did my fellowship in lymphoma, but it's been a long time since I've treated it, so I'm certainly in a days. But CD19 obviously has always been um a marker for DLBCL uh and of B cell malignancies. So I'm surprised it's not come up as a target um more recently, Craig. Is this an area you know a lot about? Has that been a relatively recent target that we've been exploring, or is it one that's been hard to drug or or what's that about?

SPEAKER_00

I don't know. So I used to co-manage patients with lymphomas when I first moved to Aubrey, Chris. So we'd present them at MDT in the city and then we'd carry out the components of care that we could deliver. So we're used to giving uh RCOP. I but I don't know the answer to your question is how long has this been in the offing, this molecule. So anyway, it's you know potentially a long time since R Chop Yeah. Close to 20 years since RCOP's been beaten in a phase three study.

SPEAKER_07

Well, that's right, long live the king, right? Yeah.

SPEAKER_02

This might have long term, so CD19 is the common CAR T target for B cell lymphoma. So that's that's interesting. I think also I'd be curious to know long term how these people do with with you know if you completely wipe out your B cells, uh, what kind of lifelong other problems people have.

SPEAKER_07

That's right. That's a weird thing about lymphoma treatment in general, Kate is why they don't do worse longer term, eh?

SPEAKER_02

I don't know if they don't. I'm just not sure that we've been following them longer. Because I think this is just a theory, but I just think we're making these people's immune system old before their time. And so are we seeing more cancers in survivors? Well, that will take a while. If they're 25 when they get their lymphoma, they might not be 50 so they get their cancer, but they may not have got it otherwise. So I'm just I'm just curious.

SPEAKER_00

Time will tell, it's very early days, but there may be a new standard challenging uh top. And then just

Negative Trials Worth Remembering

SPEAKER_00

going to finish with three negative studies. I think it's important that we do mention those. So late breaking abstract 8000, the E.COP-Acaron EA5142 study, adjuvant new volumab, post-adjuvant chemotherapy and resection of lung cancer, a negative study. Again, reiterating, we keep seeing this time and time again, the perioperative approach seems to be more effective than just giving adjuvant checkpoint inhibitors. Um, and the RAM part adjuvant study, which was a comparison of devolumab versus surveillance and devolimab plus tremilimimab in patients with high and intermediate risk uh RCCs have been resected, and that showed that the devolumab on its own didn't work. Derva and TREMI had a longer disease disease-free survival compared to surveillance. But we already know from Keynote 564 that 12 months of Pembroke had an overall survival advantage um in this population. So looks like the deverlimab's not as effective, certainly not on its own. And once you start adding in the uh CTLA4 inhibitor, of course, the risk of life-changing itises goes up. And then lastly, interesting study, abstract 5019, the Pluto study from the Canadian uh clinical trials group. This was a study designed with up de novo crossover Chris. This is men with carcate-resistant prostate cancer, the old term that we no longer use. But this was randomizing men to receive lutetium up front followed by dose taxil, or the other way around, getting dose taxil up front followed by the lutetium, and there was no difference. And so in people who can access um leticium, which is not in every jurisdiction or in every region within Australian regional patients have more difficulty accessing leticia, there's no difference on the sequence of um providing those treatments. So I just thought I'd throw that in as a pragmatic real-world study, like the one where we de-escalated from six cycles to three adjuvant peck point inhibitor.

SPEAKER_07

And did you read all of those abstracts and watch all of those sessions in your Qantas PJs, Craig, just for nostalgia?

SPEAKER_00

I did watch them in my Qantas pajamas.

SPEAKER_07

I'm glad, because that's state-dependent learning, right? So you're probably going to go to clinic now in your quantus PJs. You've taken the information your Qantas PJs, therefore you need to only be aware of it when you're in your Qantas PJs.

SPEAKER_00

And so when I get home in winter, it's nothing better than popping your quantus pajamas on. It's dark outside. And Mr. Quantas, if you're listening, we are open to sponsorship as well.

SPEAKER_07

Uh free fights. Uh, and also with all these pronunciation issues, Craig, as well. I mean, I think we're just uning for the days when the only randomized controlled trials are Etsco were full fots, fulfuria, vestum, and sataximeb, right?

SPEAKER_03

I know. The good old days. Good old days. Cases or studies won't have to do them yet. Exactamor.

SPEAKER_07

Just got a couple of quickies just to finish us off with. Um, upper

Earlier Immunotherapy In Liver Cancer

SPEAKER_07

GI 8cc, LBA 4000, Emerald 3, due to come out and lance oncology shortly. And this is inhibitor cellular carcinoma, looking at TACE versus taste plus stride. Also a stride is in a second, versus taste plus stride plus then vetnib. Now, stride is single Tremilimamab, regular interval divilimab. So one dose of TREMI and then divilimab. So now Davillamab and uh tremilimimab is a standard in advanced same resceptable post um TASE HCCs. This is bringing it slightly earlier in the uh in the setting. And this uh looked at those three arms uh and had hierarchical testing for comparing the arms. So it's quite hard in a three-arm study to work out how you're testing in what order. And if as soon as you're doing hierarchical testing, as soon as you find one particular uh comparison is negative, you don't go on and do the formal comparisons of the following comparisons, which makes it a little bit difficult. Anyone wants to compare various arms themselves, but it's just that you're not supposed to do that. The bottom line was that with um stride uh Lenva versus TACE, the um PFS was better uh with the multi-drug approach. And two-year PFS went up by 10%, which is actually quite a good gain at 10% um uh increase in two-year PFS. Overall survival was negative though, with a hazard ratio of 0.84. So not nearly as good as those studies Craig was cited where they had hazard ratios of 0.5 and 0.6. But median overall survival of only plus four months. So the um stride versus taste only, OS was not mature, hazard ratio was a bit better at 0.7. But looking at between the curves, it looks like uh stride versus taste might give you some PFS gain. I need a little bit longer to see whether that translates into a meaningful OS gain, which is statistically significant, and there doesn't look like there's a major benefit of adding Lenva, which is good because it's not a very nice drug, uh, actually. Uh so save Lenva for later in the piece. And Melanomaros

Personalised mRNA Vaccine In Melanoma

SPEAKER_07

wanted to mention abstract 9500, which is the long term follow up on NT. Endosmerin autogene, which is an mRNA individualized neoantigen therapy, where the individual patient tumour uh is sequenced and up to 34 patient-specific neoantigens are identified. They're mixed up with mRNA and they're administered to patients. And this was uh endosmerin autogene, so kind of like Sipulu cell T, which was an individualised therapy, same idea. Individualized therapy, mRNA vaccine with Pembroke in stage three, B or four receptor cutaneous disease. Um, RFS gain is quite impressive, plus 22% at four years. So that's above Pembroke alone, uh, and resected patients, quite a good EFS there. Um but uh OS encouraging trend but remains immature with a hazard ratio of 0.471. So it trends towards significant DQ trend towards events there, and immune-related adverse events appeared similar. And the

The Cancer Workforce Crunch

SPEAKER_07

um final one I want to give a quick shout out to, which is really worth um reading in this month's Lancet as well, is the Lancet Commission on the Workforce Crisis in Cancer, which was um presented in the adjacent Theatre Red to my session at ESCO. But the Lancet Commission on the Crisis in Cancer Workforce is predicting a workforce shortage of a hundred million workers um by 2050, which is a very large number. One million is very large. Uh, but nine out of ten of those were non-oncologists. Um, so they are things like primary care physicians, radiologists, pathologists, uh, and of course nurses as well. So I think it's important for oncologists as we find our clinics are getting fuller and fuller, where many of us have waiting lists uh these days as well. And as we're feeling overwhelmed, we need to reflect on the fact that actually there are many other parts of the oncologic um workforce as well, which also are under a lot of strain, and we need to tend to all parts of the garden, not just our own bushes, correct, Kate? Otherwise, we will mean that we have uh an unbalanced garden years to come. So, yeah, I think that's an important piece of work, well worth a read. There are a couple of cool commentaries that go along with that, including uh a commentary that uh myself and uh Tava wrote for uh Lance Oncology as well about the Pacific on that as well. So a great uh great presentation at ESCO uh by that theme uh and an excellent accompanying commentary uh and a fantastic commission, well worth reading. Fantastic, Chris.

SPEAKER_00

A hundred million shorter. How many people live in New Zealand? Well, there's a lot of sheep, but 5.2 million humans. Yes, so God forbid, multiply New Zealand by 20 times. Yeah, yeah, yeah. Planets could the planet cope with that. And that's the shortage of healthcare workers in Canada. Los Angeles is amazing.

SPEAKER_07

We know you're amazing, Craig, and you could probably be qualified for like about 10 million of those work.

SPEAKER_00

But we still need 90 million more. Yeah. Incredible. Okay. Wow. So that's been a bit of a cook's tour. Lots of practice changes, potential practice changes or potential new standards. This year, I think the real theme uh was around that ongoing drive towards precision medicine driven by the new treatments driven by new targets, um individualized care and patients. So very interesting ESCO overall, I would say. What do you guys think?

SPEAKER_07

Yeah, it was really good. It was good to be there. It had a different feel this year, Kate, didn't you think? Uh slightly it was a more of a hypothesis generating in some early phase stuff on uh ADCs and bite therapies, really. And lots of emerging stuff from um China in particular, I thought, which was quite a different flavor to other years. It seemed like a far fewer attendees from our part of the world. Yeah.

SPEAKER_02

Yeah, it felt to me more sensible. Like we're not just it sound feels like people are making logical decisions rather than just throwing recipes at cancer and hoping it works, which is nice. So Rakh went to a talk years ago, 20 years ago, Rakesh Jane goes, You can't just keep throwing all the drugs we have in different combinations and praying it'll work. Yes, finally being listened to.

SPEAKER_00

Fantastic. Thanks very much. Thank you, CJ, thank you, Kate. Thank you, Rachel. Did you win the bingo?

SPEAKER_01

Oh, I definitely did.

SPEAKER_00

Fantastic.

Feedback Links And Final Wrap

SPEAKER_00

So as always, invite feedback, and you can do something clever on a WhatsApp link to to send us a sound file or a typed comment. And we will talk to you all soon. Goodbye.

SPEAKER_02

Bye-bye. I'm off to have a non-alcoholic uh beer with my boyfriend. Good luck. Who is my husband? Who is also my husband?

SPEAKER_01

That's it for this episode of the Oncology Journal Club podcast, where oncology papers meet real-world practice. If you'd like to explore the papers we discussed today, head to oncologynetwork.com.au and visit the Oncology Journal Club tab, where you'll find show notes, links to the research, and a growing collection of OJC resources. Don't forget to join the Oncology Network. It's free. You can send us voice notes and chat with us on social media. And physicians, you can also claim CME points for listening to this show. This podcast was proudly produced by the Oncology Network. Until next time, thanks for listening.