The Oncology Podcast

The Oncology Journal Club Christmas Special 2024: Celebrating a Year of Cancer Research and Treatment Innovations

• The Oncology Network presents The Oncology Journal Club Podcast 2024 Christmas Special! • Season 2 • Episode 13

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G’day G’day G’day! Or should we say Ho! Ho! Ho!

Welcome to The Oncology Journal Club Podcast’s Christmas Special!

Where we take our fun and educational oncology learning resource for medical professionals to new festive heights.

Produced by Rachael Babin, from The Oncology Podcast. Joined by our esteemed hosts: Professor Craig Underhill, Dr. Kate Clarke, and Professor Christopher Jackson.

Join us as we reflect on the year's most impactful studies and developments of 2024. You'll discover the best papers of the year, the worst papers and of course, our favourite ‘blow your own trumpet' paper. You’ll also find out which host’s most listened to track of the year was by Beyonce.

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This episode is dedicated to the memory of Russell Conley. Join us as we honour Russell's extraordinary contributions, whose legacy in GI cancer research will continue to resonate for years to come.

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

Speaker 1:

G'day, g'day, g'day, or should I say ho ho, ho. Welcome to the Oncology Journal Club Christmas special, where we take our fun and educational oncology podcast for medical professionals to new festive heights. I'm your producer, rachel Babin, from the Oncology Podcast. I'm joined by our esteemed hosts Professor Craig Underhill, dr Kate Carg and Professor Christopher Jackson. Listen to discover the best papers of the year, the worst papers of the year and, of course, our favourite blow-your-own-trumpet paper. You'll also find out which host's most listened to. Track of the year was by Beyoncé. For additional insights, links to the papers and bios of our hosts, visit the show notes on oncologynetworkcomau. Season's greetings to all of our listeners. We're so grateful for your support. This is Rachel Babin signing off the last episode of the Oncology Journal Club podcast in 2024. The Oncology Journal Club podcast is produced with pride by the podcast team at the Oncology Network. Thanks for listening.

Speaker 2:

G'day Kia ora, kia ora. Welcome everybody to the end of year special, the last episode for 2024 of OGC Across the Ditch. Wow, what a year Lots of highs and lows. Dr Clark, how are you going over there?

Speaker 3:

It's hot, it's like 20 degrees.

Speaker 2:

Oh, that's like our overnight temperature here, with about 80% humidity at the moment.

Speaker 3:

Honestly, everybody's complaining about the heat, yeah.

Speaker 2:

Yeah, paul loves. And CJ, how are you? You're not in Kiwiland apparently.

Speaker 4:

Tēnā koe e te rangatira. I'm currently in Melbourne at the moment for the Adolescent Young Adult Conference here, the sixth AYA Global Congress and it's been a really well-run event Excellent MC, some great subject matter and really exciting to see the integration of people with lived experience into the main meeting as well. So a really good meeting. I'm glad to be here.

Speaker 2:

Fantastic, and I heard that you ran into one of your idols and took a selfie.

Speaker 4:

Oh yeah, mark Lewis, md. So Twitter Mark, who's a fantastic public communicator on the social media platform. He's also been a guest speaker at NZSO a couple of times. Mark's a fantastic guy, neuroendocrine patient and a GI oncologist Scottish GI oncologist living in the US so he's really a man of the world, a great guy, and it was really a real pleasure to meet him.

Speaker 2:

Fantastic. So if anyone wants to learn a bit more about Mark Lewis and his influence and his journey, eva Segalov Professor Eva Segalov gave a really great podcast interview with Mark a couple of years ago, and so let's pop the link in the notes. Rachel, I think I'd really encourage everybody to listen to that. It was probably one of the best OTC meets that we've had. Actually, it was very interesting. So we'll do that Wonderful. All right, let's get straight into it. We're going to concentrate on each of us presenting a few what we think may be the best or the most practice changing papers for the year. There's been a lot this year. I actually found it quite difficult to kind of hone it down a little bit, but before we get into that, we did have a little. We wanted to do something a bit special this end of year episode.

Speaker 2:

We want to dedicate this episode to Russell Connolly, who was the former CEO of the AGITG. So if people aren't aware, sadly Russell died of metastatic cancer a few months ago and I'm going to read from some words that Professor Lorraine Chantrell, who's at Wollongong Hospital and is the chair of the AGITG, that she used to pay tribute to Russell. You know he dedicated his life to improving outcomes for people with GI cancer and has left an indelible mark on the AGITG and its mission. Over 70 research studies were conducted during Russell's 22 years at the helm, directly benefiting more than 8,000 people with GI cancer. But the impact of these trials was felt by far more. Many of these trials were significant, practice-changing trials that changed how people with GI cancer and now treated for the better. Russell always put the patient first was crucial in the establishment of the community advisory panel. I think they were one of the first groups to do that. He also supported the launch of the Engaged Community Event Program to better provide education and support for patients and their families. When he joined in 2002, there were less than 200 members. There's now more than 1,800.

Speaker 2:

One of his key strengths was developing relationships and he grew partnerships with many local patient advocacy organizations and with the 13 other Australian and New Zealand collaborative trial groups, expanded connections outside of Australia and Aotearoa, new Zealand, into the US, uk, europe and Asia, resulting in AGRTG trials now being conducted at over 285 sites globally. He took on every opportunity to progress to your cancer research, volunteered extensive time to attend and speak at community events and more recently, played an active role in advocating for Australians with rare cancers. He openly shared his personal cancer journey to not only help others but to help raise vital funds for new research. He climbed mountains, taking on the Mount Kosciuszko Gutsy Challenge. His memory now inspires and drives us forward, keeping him forever at the heart of our purpose and reinforcing why our work to advance GI cancer must continue. So really beautiful words from Lorraine. I remember Russell is just a great guy. A lot of fun as well at conferences. Kate or Chris, do you want to add anything?

Speaker 3:

So from this side of the straight, yeah, gentle but hilarious little sparkle in his eye and I just want to use a whakatauki that I think many New Zealanders will remember so kuahinga he tautara I te wāo nui a tāne. So a tautara has fallen, which is a large, beautiful, large tree from here has fallen in the forest of Tāne, and it's just a way of expressing how his life meant a lot to a lot of people and it's over far too soon.

Speaker 2:

That's beautiful. I'm not going to try and say the word. How did you say it, Kate?

Speaker 3:

Oh, whakatauke, whakatauke. Just a useful saying that has all of that power in it.

Speaker 2:

Yeah, great.

Speaker 4:

Chris, yeah, russell's been at the helm of AGITG for a very long time. He was just an absolute servant to the organisation and he grew alongside the organisation over the course of the last 20-odd years. There wasn't an AGITG event that Russell didn't attend and he was sorely missed in his medical leave over the last couple of years. Real personality, real character and has steered us through the growth of the organisation. Russell was a close friend as well as a staff member, obviously a close friend to many in our community and will be deeply, deeply missed.

Speaker 2:

Yeah, I don't know what he'd say at this point. Okay, enough, guys, on with the show. Probably so, kate, do you want to kick us off with your thoughts on some of the best or most practice-changing papers for the year? Yeah, kate, do you want to kick us off with your thoughts on some of the best or most practice changing papers for the year?

Speaker 3:

Yeah. So look, I'm going to start with the one where I'm stepping out of my comfort zone into gynae, but it's just yet another of the epidemiological studies that's demonstrating the joy, within the gynecological community, of the HPV vaccine. This was looking particularly at very young women, who, sadly, can still die of cervical cancer, so women under 25. And since, excuse me, from 1992 to 2021, the rates of cervical cancer and, more importantly, cervical cancer deaths have plunged by 80%. So that's a win, and please get your young people vaccinated when it is available to them.

Speaker 2:

I just wanted to highlight as well, because this is one I had on my short list, and that was the INTERLACE study induction chemotherapy followed by standard chemo radiotherapy versus standard chemo radiotherapy alone in patients with likely advanced cervix cancer. So that showed a benefit for this short course induction chemotherapy with affordable drugs, and so that's the significance of this paper. I think it will change practice, probably globally, and this is not with immunotherapy or an expensive targeted therapy. This is with relatively affordable and cheap cancer care. So the reason for mentioning this is probably a significance in the lower and middle income countries because this is a new treatment involving immunotherapy not involving immunotherapy or an expensive targeted therapy, but with relatively affordable drugs. We were lucky in the upper income countries that we have vaccines and prevention programs that are often sadly lacking in the lower and middle income countries, so this is a sort of globally significant paper.

Speaker 4:

Craig, any thoughts on why neoadjuvant chemotherapy followed by chemo-IT was positive, whereas chemo-IT followed by adjuvant chemotherapy was not?

Speaker 2:

I think it probably may come back to the biology of cancers. There's still some thoughts that kicking off with radiotherapy actually may not be ideal. You should go with the chemo first, in terms of radiobiological hypothesis, but also maybe that the chemo is quick to deliver and give access in a much quicker way than referring and planning for radiotherapy et cetera. So it might be that you're getting the treatment early. I don't know.

Speaker 3:

I worked in this unit at UCLA some years ago, 2008, 2009. And Mary is a force to be reckoned with Professor Mary McCormick. She's a gorgeous woman. I too am curious and I do wonder whether it is some of the practical issues, but I haven't looked in depth at the paper. This is not a disease I treat anymore, and it is easier to get started on chemo than it is to get started on radiotherapy. But if you think about things like rectal cancer, we're always debating this order of chemo-rad versus chemo and coming up with the exact opposite. If you look at the OPRA, chemo radiotherapy followed by chemo seems to be the preferred strategy. So I just, you know, I think, watch the space. We still don't really really understand 100% what we're seeing, but this is randomized, well-controlled trials. I have had conversations with radiation oncologists locally who are concerned that the radiotherapy is out of date, quote unquote. But that's the nature of trials, sadly. So they both sets of people got the same radiotherapy. So you have to say the chemo did add to the radiotherapy that they got.

Speaker 2:

Yeah that's right. If the question was does the chemo add? It did, and it was five years. Overall survival, 80 versus 72%, so a meaningful magnitude benefit hazard ratio 0.6. Well 100%.

Speaker 4:

And the accessibility issue is really quite critical too, craig, given that cervical cancer is largely a disease of low and middle-income countries still Obviously still present in high-income countries, but much more so low and middle-income countries. So it's critical to be designing trials in ways which are accessible and affordable. But hopefully it will be a sunset disease.

Speaker 2:

Kay, what else have you got for us?

Speaker 3:

Yeah, so my next one is the Chilabi paper, niche 2, which is the DMMR colon cancer patients who were given one dose of IPI, two doses of NEVO, with pathological complete response rates of 68% and major pathological response rate of 95%. We debated this at the time. You know what do we actually do with these patients. The vast majority of DMMR patients are going to need their whole colon out anyway if they've got Lynch syndrome, et cetera, et cetera. So you know where to put the starter is interesting, but definitely in the locally advanced patients who would otherwise have to have very morbid surgery, this provides something that's really useful and, again, genuinely affordable, because there's not 12 months worth of immunotherapy afterwards.

Speaker 2:

Yeah.

Speaker 3:

And are you able to access this in New Zealand outside of a study? I can access it, but only if the patient can fund it.

Speaker 2:

Yeah, okay, yeah, very nice.

Speaker 4:

Which dose of IPI was that, Kate? Was that IPI 1 or fixed dose IPI it?

Speaker 3:

is IPI 1, I think. But watch this space. Sorry, I apologise to the producers. There will now be ruffling of papers.

Speaker 2:

So Chris kate's doing that.

Speaker 4:

I'd see that you also had an immunotherapy in um msi high medicetic colorectal cancer is one of your practice changing papers. Yeah, that's right. That was the uh checkmate, uh hw, which is um unusual because it's not checkmate bunch of numbers, it's checkmate bunch of letters and numbers, which is an innovation in and of itself. This is a phase three, three-arm study in stage four, dmmr colorectal cancer, of whom 26% had BRAF mutations as the reason for the DMMR, which is lower than I see in clinical practice, and the patients were randomized two to two to one to receive either IPI1,VO-240, or NEVO or chemo, and the chemo was dealer's choice, doublet plus or minus a biologic. It was an unblinded study which will impact, of course, on interpretation, with a primary endpoint of progression-free survival.

Speaker 4:

But if you get a moment, take a look at these PFS curves because this isn't sort of credit card between the PFS curve stuff. This is very much a very large American-sized Humvee vehicle between the curves with a 24-month PFS with immunotherapy of 72% versus 14% with chemotherapy. Grade 3-4 AEs were actually lower with ipinivo 23% than 48% with chemotherapy, although the AEs do appear low. It's frustrating to me that ipinivo versus nevo hasn't yet been reported and it may entrench ipinivo as a standard of care when in actual fact, you know, many of us would be using pembro monotherapy in this situation, are interested to see what the relative benefit of the IPI 1mg per kg is. So that is still to be confirmed, but I think IPI-Nevo or Pembro are standards of care and I think that chemotherapy is now not a standard of care in DMMR.

Speaker 2:

I think we'd all agree with that, and we just need to make these treatments accessible. Kate, was the dose of IPI 1mg? It's just the 1mg per kg, just once, the same as the Andre paper that Chris just talked about. Fantastic, kate, what else have you got? You must have something in breast cancer, for sure.

Speaker 3:

I do so. My third paper is the Sonia paper, which is looking at half of a group of women who had metastatic hormone-positive breast cancer who were given. All women were given aromatase inhibitor in the first line and fulvestrin in the second line. Half were given Pelbo with their first line of endocrine therapy, half were given a CDK4-6, mostly with Pelbo in the second line setting. The primary outcome was PFS2, so how long it took them to get to the end of the second strategy and there was no statistical difference at about 30 months in both groups. And more importantly, those women who got the second line CDK4-6 were on the second line CDK4-6 for only eight months as opposed to 25 months in the first line, which is about a third of the price.

Speaker 3:

So I was delighted by this trial. By the virtue. It's very practical and pragmatic and cost-saving. There will be detractors who will say that most people are on palbocyclob and there is discussion about whether that is as useful as the other ones. But again, I think that is obfuscating. I think this is really useful data. Interestingly our special authorities, so our equivalent of the PBF, makes this strategy quite tricky. You have to misinterpret a tick box currently to get second line CDK46.

Speaker 2:

So the CDK46s are in routine care in New Zealand now in the advanced setting. What about adjuvant no, no?

Speaker 3:

We've had them in the advanced setting since April 2020. But we do not have them in the advanced setting. What about adjuvant no? No, we've had them in the advanced setting since April 2020, but we do not have them in the adjuvant setting.

Speaker 2:

Yeah, there was quite a lot of advances in breast cancer this year. Actually we don't have time to go through them all, but it's becoming more and more niche in the subgroups of patients. Biomarker-directed but small but meaningful gains in various subgroups of breast cancer.

Speaker 3:

Yeah, look, the three of us are GI oncologists, so we all have our biases, but I think we're getting there in the GI world too. We're just a little bit slow off the mark, but we will get there.

Speaker 2:

Yeah, great, chris. I see you've listed Nadina, so melanoma, I had this on my short list as well, but please, steal my thunder.

Speaker 4:

So the Nadina study the general theme to the studies that I've got as my picks of the year are actually all academic studies, so they're led by academic investigators who structure their studies in such a way that are answering really important questions that are clinically meaningful in a way that is really informative, and so kudos to academic investigators and for their leadership. And Nadina was a study in stage three melanoma, a preoperative study of two cycles of ipi-nevo, so ipi-80 and nevo-240, two cycles followed by surgery at week six, and those were stage three melanoma versus 12 months of adjuvant nivolumab. The study was really nicely designed in that after two cycles of ipinevo and then surgery for axillary clearance, that group had their nodes reviewed and if they had a major pathologic response or a complete response, they got observation. So that means that they only got six weeks of IO or two doses of IO. Those who did not get a major pathologic response are more than 10% of tumor cells left behind. If they had a BRAF mutation they went on to dabrafinib, trimetinib, and if they didn't have a BRAF mutation they carried on with the Volumab. Now that strategy hasn't been tested formally, but it is exactly what you would want to do if you were reading the tea leaves and thinking well, it didn't really get much response, what should I do? Should I switch those to BRF inhibitors? So I thought that was a really nice and a brave design when they did that and the standard of care run was 12 months to volume up, which of course couldn't be adapted to response because all the disease had been taken away.

Speaker 4:

The primary endpoint was event-free survival, which is not the best endpoint for a neoadjuvant or adjuvant study. It needs to be overall survival. But EFS of course reports much sooner than OS and the improvement in event-free survival was a whopping 26.5% increase in 12-month EFS with the investigational arm, 26.5% improvement in the EFS, and that's on top of a 10-15% DFS gain you get with IO. So it's a thick end of 40% above surgery alone, really, really with the use of IO in total. So that's huge. Interestingly, the gain was actually slightly more in those with BRAF mutations compared to BRAF wild types with the pre-op IO approach. So it's still suggesting that we should, even with BRAF mutants, should still be using this IO-based approach. So I think that was practice changing for many people, even though it's EFS data only. I'll say that again, adjuvant studies need to be OS, but 26% 12-month EFS oh my goodness. If that doesn't translate to an OS gain in due course, then I'm very, very, very happy to see the Australian National.

Speaker 2:

Government. Oh my goodness. So I presume that OS is being collected but just not reported yet? Yeah, that's right, collected but just not reported yet. But you second me on that? Yeah, that's right. Can we just note that down, please, rachel? Chris will sing the Australian national anthem. If it's not positive data and I just want to know December 2024,. Professor Chris Jackson of New Zealand advocates for one of the best papers of the year to have a primary endpoint of EFS in the adjuvant setting capitals, all capitals. Oh, he's speechless. He's standing by 2024. The rest of the specs of New Zealand is speechless.

Speaker 4:

Yeah, that's almost more of a landmark, craig, actually, me having another say no, look. I think it's a really beautiful study. I really admire the MIA for the way in which they've pushed our uh field forward over such a period of time. They've taken risks in in their study design and I just really admire their work. It's taken us so far in such a short space of time.

Speaker 4:

You know, when I started um treating melanoma, when I first became a consultant, we were using dtic with no enthusiasm, you know, and to see us here with a plus 40% gain in one year, efs is just it's mind-boggling. So I think that these new approaches should be incorporated into paradigms and New Zealand will be putting forward to our regulator that they should be considering the pre-operative approach as opposed to the adjuvant approach because of the pharmacoeconomic position of that as well. But the two cycles of pre-op is almost certainly more cost-effective as well, even with that preliminary data. I think if you pop that through the ESMO Matitude of Clinical Benefits scale you would see that would come out pretty well. I haven't done that crunching, but ESMO acknowledges that EFS and adjuvant studies does warrant a good score, although OSs, of course, were advantageous and Speechless do a really great comeback.

Speaker 2:

Well done, chris. I decided to go on to Blue Sky and ask people what they thought was their best papers of the year and had a few replies and one I put out there that maybe Top Gear we should cover. And then Lizzie Smythe at Oxford, who's also been on the podcast before click on the link, came back and said if you're talking about SIPAC, you should cover Top Gear. So I think I thought, chris, that you're no doubt would be interested in covering those they're accentuating the concept of sometimes less is more.

Speaker 4:

Yeah, so we covered Top Gear just in a recent podcast and you can listen to the more detailed analysis of the Top Gear study. But I'll go over that one very quickly because it's a trial of what not to do rather than what to do. Top Gear was the AGITG-led study by local luminary, trevor Leong, of preoperative chemo radiotherapy with chemotherapy in gastric and GOJ cancer compared to perioperative chemotherapy alone and that used chemotherapy with radiation preoperatively followed by surgery, followed by chemo, compared to the standard arm, which was magic chemotherapy or ECF, which was updated to FLOT when the FLOT4 study came out. New England Journal of Medicine study bottom line a plum negative study. Median overall survival 46 versus 49 months, no difference. Still a gain over CROSS in terms of median overall survival, which is interesting, and a gain over magic, which was the pre-operative ECF, which had a 36-month overall survival. So we are incoming and getting better, which may be stage, migration may be better, staging may be better surgery. So the outcomes are getting better for gastric cancer and top gear than they were in MAGIC with control arm doing better. So that's off note, but certainly it confirmed in that study that chemotherapy rather than chemo RT was the way to go.

Speaker 4:

Moving on to the ESOPEC study. This was presented at ASCO this year. This was a study in esophageal cancer which the background to this is that TROS chemoradiotherapy with carboplatin and peclatexil, followed by 41-grav radiotherapy so lower than had been used in the previous esophageal studies, versus surgery in predominant adenocarcinoma of the esophagus but with 25% of squamous cell carcinoma, showed that that approach was superior to surgery as a standard. That was the CROSS study. The FLOT study was four cycles of FLOT followed by surgery, followed by four cycles of FLOT, and that compared to MAGIC and that was better. So that was a comparison of those two. Now, cross was a predominant esophageal, flot was a predominant gastric study and this is esophageal NOGJ and no carcinoma.

Speaker 4:

Only Worst characteristics in this study an esopec of all the tumors with 7% T4 compared to none in the CROSS study. 80% node positive in the study compared to only 65 in CROSS. And impressively, a mere 91% of patients in CROSS completed the full treatment, compared to AMIA 75% in ESOPEC. So really low treatment completion in ESOPEC. And in ESOPEC only 83% went on to have surgery, so again really low.

Speaker 4:

The landmark for achieving surgery in esophageal should be 90% plus. So that was a worry. But three-year overall survival was better with FLOT at 57.4% compared to 50.7% with CROSS. Median overall survival of an amazing 66 months with FLOT, compared to 37% with the CROSS approach. Preoperative morbidity was similar. So people have taken this to mean that FLOT should be the standard of care in resectable esophageal and esophagogastric junctional cancers by and large. But I think the critical point for me remains that patients still have to get to surgery to get the survival gain. And FLOT for some patients is just too toxic because it involves good doses of oxaliplatin and texanes, so you do have to be robust, whereas CROSS is a much better tolerated regime in our hands and in our institution. If we only got 83% of people to sorry, 75% of people through all the cycles and 83% to surgery, then we'd be doing very, very badly indeed.

Speaker 2:

But it's fair to say the standard of care now is if patients are fit, they should be considered for FLOT, not chemo or radiotherapy, correct, yeah, so for FLOT patients, this has some huge resourcing implications and you know we talked in the last episode about people who need to relocate for many weeks at a time to receive radiotherapy. They don't live in a metropolitan area, so this has a lot of practical implications as well. So Professor Neil Tebbert from the Austin Hospital in Melbourne, living in John Kensington, went further and actually suggested suggested that GI Radonks didn't need to bother going to upper GI MDTs anymore. But that's probably a little bit of a radical statement, but nevertheless, two landmark studies and kudos to JCO and New England Journal for publishing them. But you know, negative studies often don't get published and this one was, and I think these ones were and I think will have a major impact on standard of care.

Speaker 4:

Yeah, it's a bold call to say that radiation on colitis shouldn't attend the GIMDMs anymore, particularly in the upper region, but certainly their role has narrowed somewhat, and we certainly would still consider CROS for patients who had marginal fitness or no negative earlier stage tumours, rather than adenocarcinomas of T3 slash 4 in bus. And of course we've got the squamous cell carcinomas to consider too, which is still a population of notes that we still have to consider, even though adenocarcinoma is a predominant histology in the western populations. And, craig, just your point about the radiation being resource-hungry. Of course many people in low and middle-income countries don't even have access to radiotherapy, and radiotherapy requires quality control as well, and so good radiation therapy does need to have good planning, and chemo is more deliverable for people in lower resource settings. So it is pleasing to see that that is an effective and appropriate treatment for that group of patients.

Speaker 3:

Look, I think the other thing too is I have, and maybe I'm just getting old, but I do think there's a different.

Speaker 2:

Getting, what do you mean? Getting old?

Speaker 3:

It is. I'm still younger than you. What I am seeing is and I was just talking to a colleague today is it that people are getting younger or is that my idea of young is changing? But there is a group of young women with squamous cell esophagus that we are seeing that I swear we didn't see 10 years ago. So yeah, I think there are still squamous esophagus people with squamous cell cancer of the esophagus who require treatment, and still the standard of care for them is definitely a triple modality if they are well enough for it. And these women are in their late 30s, early 40s, and that is the argument.

Speaker 4:

All right, I think the only other practice-changing articles in GI cancer this year have been the plethora of articles of TNT and rectal cancer. Of course we had the Rufido updates, we had the Oprah updates and we've covered those on earlier podcasts. And so for detailed discussion on those, go through the back catalogue of OJC articles and add to our listeners, because it can't just be me listening 400 times to drive up the subscriber count.

Speaker 2:

All right, I want to change track a little bit and just feature a couple of papers from the realm of targeted therapy. So the first one is Alena, which was electinibine resected ALK positive non-small cell lung cancer, so adjuvant study. In the past platinum-based chemotherapy was a recommended standard and this was a study comparing that approach with oral electinib 600 milligrams twice daily for two years. Primary endpoint was Chris, was it overall survival, disease-free survival? And other endpoints included CNS disease-free survival, overall survival and safety. So we have a report of the disease-free survival. There's only been six events in the survival analysis, four in the chemo arm, two in the elective arm. But the disease-free survival curves, as you mentioned before, these are not put to credit card between the gap, these are drive a truck through the gap and so the percentage of patients alive and disease-free at two years was 93% in the electinib group versus 63% in the chemotherapy group. These were stage 2 or 3a resected disease. So the hazard ratio is 0.24, which is incredibly impressive. Cns disease-free survival was also compared and 0.22, as I said, the data for overall survival was immature. Just of note, about a quarter of patients needed a dose reduction. So some of the toxicities include GI toxicity and we've mentioned many times before that even a fairly low-grade toxicity when you're taking a drug for two years every day can be quite significant burden on the patient. But nevertheless I think this has become being embraced as the new standard of care for this subgroup of lung cancer patients.

Speaker 2:

And then another targeted therapy. This is trastuzumab-deruxtacan, which we've seen some advances in breast cancer. Of course this is a HER2-directed antibody drug conjugate which is now in widespread use in breast and gastric cancers. And this was a study, the DESTINY-02 phase 2 trial, which was in other cancers. So there was 267 patients endometrial, cervical, ovarian bladder, biliary tract, pancreas and some others. It was a median follow-up of 12.7 months. Overall response rate was 37%. The progression-free survival 7 months. Median overall survival 13 months.

Speaker 2:

These are patients who failed other therapies. So it's only a phase 2 study, but I think it's highlighting that you know we're going to have more and more of these targeted therapies that won't be just in for the anti-HER2s, won't just be in breast cancer. So again, I put this on our proposal on OncSky on hashtag OncSky on Blue Sky, and Jenny Liu from Sydney came back and was proponent for discussing this study because it's the first FDA tumor agnostic ADC approval, ushering in a new era for quantitative IHC assays, independent of histology, to guide precision oncological treatment. She says but we need panel proteomic assays. So thanks for that comment, jenny. I know that she's an avid listener of the podcast.

Speaker 4:

Chris, great Tumor agnostic approvals. You know you're going to have to do a bit more work to convince me that's a good idea. If you look at things like B-REF inhibitors, for example, I mean, the response to those is very, very, very from tumor location dependent colorectal versus melanoma, for example and if we had tumor agnostic approval of BRAF inhibitors we'd be nowhere with those. So I'm really concerned about that notion and worry that it's actually a push for people to circumvent doing the detailed number of trials that's required, and so I must say I'm very anxious about that as a strategy. Do you have any reflections or comments on that? In other words, do you agree with me? I feel like a little bit of a conference question at that point in time.

Speaker 3:

You would remember that we spoke about the ESMO framework for tumor agnostic potential of cancer therapies, which divided up tumor agnostic, tumor informed and tumor specific targets.

Speaker 3:

So we can go back in the back catalog and have a look at that paper, and the authors agreed with you that there are targets and there are targets. I think I would also stress that as an oncologist, particularly as one who works in an increasingly narrow sphere of cancers, that understanding the toxicities of a drug that has crept into my sphere without me getting the normal practice at it, for want of better expression, is a challenge in and of itself. So a GI oncologist who is giving trastuzumab to ruxetan on occasion needs to be very careful that they are following the toxicity guidelines that the breast cancer teams have created, because it is not an untoxic drug and it needs careful monitoring and people can get very sick very quickly and, for reasons we don't understand, the toxicities, particularly pneumonitis, seem to be higher in GI cancer patients than we see in breast cancer patients. So don't disagree with you, chris, but as always, I turn a sentence into an essay.

Speaker 2:

So there you go, yeah it's a watch this space, but I think it's a very interesting field, chris. So I have one more to mention, and this was suggested by, I believe, a trainee, a medical oncology trainee from Sydney, dr Matthew Wilson, who said I should include Harmony 2. So I'm going to thank Matthew for commenting. This was a study using a drug called Ivoniskimab which outperformed Pembrolizumab as frontline therapy in PD-L1 advanced non-small cell lung cancer, presented at the 2024 International Lung Cancer Society World Conference on Lung Cancer.

Speaker 2:

This is a new drug developed in China. It is a combination of PD-L1 inhibitor and VEGF inhibitor and there was a randomized phase three trial comparing it to upfront PEMBRO and showed response rate better. So there was no mature overall survival data shown and the discussant concluded that some more follow-up and more studies were required. But it's an interesting new molecule that's been developed and I'm sure there's going to be lots more trials conducted in this space. But if we have, you know, there's a lot of patients who do receive single agent PD-L1 inhibitor upfront, and so if there's already now like a second generation combo, it'll be interesting to see whether that displaces Pembro in the advanced lung cancer setting. Chris.

Speaker 4:

So, craig, with that agent you say it's a combined PD-1 and VGF toning agent, right? So what was the experience with VGF agents in lung cancer, because of course, we've been through the VGF era and the noughties? What was the experience with VEGF agents and lung cancer, because, of course, we've been through the VEGF area, we've been through the VEGF area and the noughties. What was the experience with that?

Speaker 2:

Some regimes do include bevacizumab, but there's some analysis suggesting that maybe the additional benefit of that is small. So we can dig up those papers and put them in the notes as well. So it's controversial. Does it really add anything? It's hard to know, but VEGF inhibitors do seem to have some activity and role in advanced non-source cell lung cancer.

Speaker 4:

And certainly, for example, in HCC. Combined atezobiv, for example, targeting the combined VEGF PD-1 pathway in that cancer seems to be efficacious. There's also some suggestion that the same may be true in melanoma also. So you know, combination VGF-PD1 does seem to be relevant. Any interesting sub-studies there on the microbiome, craig?

Speaker 2:

Oh well, I think this could. Yes, well, I think you know this could be the blow your own trumpet Paper. It in the air, which was, of course, Ashrae Gunja was the first author and I was lucky enough to be included as a co-author. Study published in Nature Medicine a gut microbial signature for combination immune checkpoint blockade across cancer types. So you know, we know, there may be a link between gut microbiota and response to checkpoint inhibitors. So this paper demonstrated that there is potentially a cross-cancer and cross-country validity of a strain response signature, so specific microbiome strain that is associated with response, common across cancers and common across countries.

Speaker 3:

Is that a strain strain?

Speaker 2:

Yeah, strain In.

Speaker 3:

Australia yeah.

Speaker 2:

No, it was in multiple countries. It might have even been in New Zealand patients. So this was a study done in rare cancers using ipinevo. It was a translational study, sub-study out of that. So I think it was a translational study, sub study out of that. So I think it was a very interesting paper, and you know it's teasing again. Do we need to do some work in um microbiome gut, microbiome diagnostics or therapeutics to be able to tailor treatment regimens according rather than according to cancer type?

Speaker 4:

yeah, I think that's think that's a great study, Craig, and congratulations on such a prestigious publication. I must say Well done.

Speaker 2:

It's been a major cited paper papers I've been co-authored on this year that one stands out as the one that's been cited the most number of times already in other publications.

Speaker 4:

Noel, congratulations. I think clearly the microbiome is important for response to IO. Exactly how will be interesting, and I would be willing to wager a second verse of the Australian National Anthem on the fact that the microbiome is going to be important in the etiology of early-onset GI cancers as well, which, of course, we're seeing a slight small but significant uptick in those over the course of the last decade also. So I'm sure that microbiome is going to be a part of that. So shout out to all our fantastic microbiome researchers out there. Look forward to all your hard work, uncovering all these problems for us to talk about on our forthcoming podcasts fantastic and an interesting worst.

Speaker 2:

I picked one that was like the worst paper I could find of the year and this is in the context of what's going on in the us and the drug and the regulatory agencies and the health agencies there. But it was a study published in the oncologist suggesting that a homeopathic treatment as an add-on therapy may prove quality of life and prolong survival in patients with non-small cell lung cancer. And now it's been retracted and so there's a thing called Retraction Watch and they went through and basically showed that it was fraudulent paper and so it was retracted. But I do worry about a push for treatments like homeopathy in the years ahead.

Speaker 4:

Kate, didn't you cover this year a paper which looked at people who opted for non-standard versus standard therapies? Do you want to quickly recount that one?

Speaker 3:

Yes, I think it was in breast cancer, but sadly, both at the curative end and people with more advanced disease live shorter and lower quality lives if they pursue alternative therapies as opposed to alongside over-ended therapies. And I think there's some goodness I wish I could remember her name who wrote beautifully about how difficult it is for patients to navigate the amount of information that is available out there and to choose what to trust. And a skill in what we do as medical oncologists is to help guide people through those decisions in a way that they can engage with.

Speaker 4:

Yeah, really important to ensure that people have good access to high-quality information, that we had good access to high quality information that we can do to debunk false information out there as well. Also an important reflection, I think, for Indigenous communities actually, that the incorporation of Indigenous medicines do seem to improve cooperation with traditional Western collaborations, seem to enhance completion of more Western-based therapies. That was some data which I was seeing at the AYA conference this week, presented from Canada, which I thought was really interesting. So I think it is important to look at Indigenous models and sharing care there, so not being closed to that, but I think quackery is a different step there as well, as opposed to culturally appropriate care.

Speaker 2:

Yep. Now Obama does on Twitter. He does like these groovy holiday playlists, so I want you all now to pick up your iPhones and go to your playlist of the year. And, Chris, what was your most played song for 2024?

Speaker 4:

Look, I was a bit worried that Barack Obama came up with playlists when he was still in office. I thought, geez, I'd rather you were running the US than listening to Spotify. But anyway, my top song of the year was, shockingly enough, in line with my Twitter bio, which is Radiohead, tragic and my top song. I think my top five songs were actually all Radiohead songs, but this year my top Radiohead song was Weird Fishers, which is a fantastic song from Radiohead's best album, and Rainbows, which is a fantastic song from Readyhead's best album In Rainbows. In my opinion, are these new? No, not at all. In Rainbows is one from 2007, 2008,. I think. Brilliant album, beautiful album. And Billie Eilish features highly in my playlist too, and I think, craig, she was one of your tops as well, wasn't she, billie Eilish?

Speaker 2:

It was. My top artists were Beyonce, billie Eilish, troye Sivan, ariana Grande and the Cure. So the Cure made a late run. They've got a new album out which is reslashingly fantastic. It's like Disintegration Part 2, and it's all about the end of their career and the end of their lives. It's really fantastic.

Speaker 4:

So the Cure, lamenting their success for the duration of their career? Oh, my life is so terrible. I lives. It's really fantastic. So the cure, lamenting their success for the duration of the career. Oh, my life is so terrible. I've been so rich and successful.

Speaker 2:

Now I'm coming to the end of it and they, um, it was very good, and the others are from the influence of my, um, my daughters. But yeah, beyonce, the my favorite song, most played song, was amen by beyonce, which is the ice track on carbocada, which is very bleak outtake on American politics. And then number two, billie Eilish the Greatest, which is a fantastic song. Kate, what about you?

Speaker 3:

So I've been into Frank Turner more recently, so my favorite song is Undefeated has the line in it autumn is sometimes the prettiest time of year and maybe that's just my perimenopausal nature, so I love that. And then my second favourite song is she Speeds by Straight Jacket Fits which Dunedin sound. So for Australians who haven't heard it frickin' brilliant song, best description of a woman ever. And have a listen. And that sound you're hearing is the Dunedin sound and you need to get across more of it Beautiful trick, kate, beautiful trick.

Speaker 4:

We better watch out, otherwise the Australians will start claiming straight jacket fits as well.

Speaker 3:

Yeah, I'm going to the Australian group Crowded House next week in Melbourne. I've already seen them because they played here first and it was brilliant. Was it good? Absolutely brilliant. Yeah, absolutely brilliant. We were standing up by the end of it.

Speaker 2:

We got last-minute tickets, I think they were. I didn't realise they were playing in Melbourne. I think it was tickets that are set up. You know, once they had the stage set up and they're right at the side, which is the only time I've ever seen them was like that. So it felt appropriate. And Private Universe is special. It's like our song for my wife and I, so looking forward to going to see them next week. Rachel, thank you for all your hard work this year.

Speaker 1:

It's an absolute pleasure.

Speaker 2:

Do you want to tell us what your most played song was?

Speaker 1:

Well, my most played song was Rising Appalachias. I believe in being Ready, but the rest of my list, I'm afraid, has been hijacked by my seven-year-old. So there's quite a lot of Taylor Swift and Dua.

Speaker 2:

Lipa.

Speaker 4:

Nothing wrong with that right, that happened to me one year and I had to actually get family Spotify in order to keep the kids out of ruining my recommendations, otherwise I was going to get you know, crazy Frog. And so and someone popping up randomly on my must-listen-to list- yeah, Disney songs, Matilda.

Speaker 1:

the musical songs feature heavily.

Speaker 2:

I like them All right. Well, I'm looking forward to listening to those tracks that you all mentioned. I think we should do a podcast on music. It sort of suddenly was everyone, the conversation was much more exciting and talking about targeted therapy. So happy holidays, happy end of the year to all of you and to all of the listeners. Thanks to everyone for their support this year. It's been great and to be growing the listenership again, send us in any suggestions for papers. I had got approached by someone at COSA who wants to come on the podcast and do an interview, so we'll have some new, exciting things in 2025, batten down the hatches. 2025, here we come.

Speaker 4:

Can't wait, Medi-chemity everyone.

Speaker 3:

It's 22 degrees now in Wellington. People will start dying shortly. Matiwa.

Speaker 2:

Dearing me. All right, good on you. Happy Christmas, everybody, yoda. See you next year.

Speaker 1:

Thank you. 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. Thank you.