Highlights from ASCO 2024

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Showcase of AGITG research | Research partnerships |
Lower GI research highlights | Upper GI research highlights | Translational research highlights

 

This year, the theme for the ASCO Meeting was The Art and Science of Cancer Care: From Comfort to Cure.

Image of Rob Ramsay in a speech bubble.

Rob’s observations

Another ASCO has been completed, but the impact of several key studies will endure. The same phenomenon of replicating a huge ant colony with the tens of thousands of delegates streaming in all directions was in full display again this year. Not too many masks were evident, but the legacy of COVID-19 permeated talks and posters.

Thank you to Louise Christophersen, Prof Tim Price, Prof Rob Ramsay and A/Prof Amitesh Roy for providing these highlights.

 

Showcase of AGITG research

Research by the AGITG has had a strong presence at the Meeting this year.

Dr Belinda Lee presented the final abstract for DYNAMIC-Pancreas, a pancreatic cancer study. DYNAMIC-Pancreas investigated the usefulness of ctDNA as a biomarker in informing clinicians of a patient’s risk of disease recurrence and guide treatment decisions.

The study team found that using ctDNA is a feasible approach to determine which patients with pancreatic cancer should receive chemotherapy after surgery to remove their cancer. ctDNA detection was associated with earlier recurrence, but analyses of the impact of changes in ctDNA over time on survival are ongoing.

 

A woman with black hair and pink clothing stands in front of the ASCO photography background.
Dr Belinda Lee interviewed by ASCO Post.

 

Watch Belinda’s interview

 

Two other AGITG studies were presented as posters at ASCO this year: MONARCC and Neo-CREATE.

The MONARCC trial, led by Dr Matthew Burge, investigated the potential of using a ‘lower intensity’ chemotherapy in combination with a targeted anti-cancer drug in elderly patients with colorectal cancer. This treatment was compared with using the targeted drug alone.

Usually, older patients cannot tolerate standard treatment therapies due to the toxic side effects. This study found that either of the strategies tested here might be better as first-line options for these patients. This trial was supported under an AGITG 2015 Innovation Grant.

 

Professor Chris Karapetis with the MONARCC poster at ASCO.
Associate Professor Amitesh Roy with the Neo-CREATE poster at ASCO.

 

The Neo-CREATE study, led by Associate Professor Amitesh Roy, aimed to assess the safety of adding immunotherapy to chemoradiation, given before surgery to remove the tumour, for people with gastro-oesophageal cancer.

They found that combining a checkpoint inhibitor to standard-of-care chemoradiation was safe and feasible in these patients, but didn’t offer a significant advantage over standard treatment.

Image of Rob Ramsay in a speech bubble.

Rob’s observations

I am not a clinician, so my views of what is important may not be fully shared by my colleagues and I do have an enthusiasm for certain areas of research. Nevertheless, I think most would agree that immunotherapy is not going away and indeed is shifting the bar where new benchmarks are being set for future trials to compare to.

 

Research partnerships

In attendance this year was AGITG Clinical Development Lead, Louise Christophersen, who facilitated in-person discussions between AGITG leadership and other groups.

“It has been an incredible experience attending ASCO 2024 and seeing AGITG’s research receive so much interest,” says Louise.

“Seeing Dr Belinda Lee present the research findings of the DYNAMIC-Pancreas study to a worldwide audience was exciting. Equally as exciting were the poster presentations of the MONARCC study by Prof Chris Karapetis and the Neo-CREATE study by A/Prof Amitesh Roy. The audience was engaged with the research, which indicates that we are conducting and endorsing research which is of interest to the academic community.

“One of our priorities this year was to meet with new and existing industry partners, as well as collaborative international research groups. We recognise that these face-to-face meetings are invaluable for building and sustaining relationships, often unlocking new and exciting opportunities for mutual collaboration in GI cancer research.

“In total, 12 productive meetings were held throughout ASCO, and I would like to sincerely thank the AGITG leadership who actively participated during each of these meetings.”

Image of Rob Ramsay in a speech bubble.

Rob’s observations

ASCO is a meeting embedded with meetings and that was the case for AGITG too. Chris Karapetis, Chair of the SAC, led a string of meetings organised to the minute by Louise Christophersen. All were designed to increase our connections with industry, source access to drugs and most importantly cement our relationship with other like-minded clinical trials groups from old friends in Canada and newer friends from Ireland.

 

Lower GI research highlights

Professor Tim Price, Lower GI Working Party member and Study Chair for Neo-POLEM, was also in attendance and noted the standout role of surgery this year, particularly liver transplant surgery.

The TRANSMET trial found that the five-year overall survival for patients with liver metastases of unresectable colorectal cancer skyrocketed from 13% with chemotherapy alone to 57% with liver transplantation and chemotherapy.

“For the first time, a trial reported a potential benefit of liver transplant for a highly selected group of patients with liver-only involvement of their colorectal cancer,” he says.

A lower GI cancer trial to watch, according to Tim, is the follow up to ARC-9.

“The results presented at ASCO suggest a new potential treatment option for patients who have had prior standard chemotherapy,” he says.

“The agent is etrumadenant, which is a A2a/A2b adenosine receptor antagonist.”

Image of Rob Ramsay in a speech bubble.

Rob’s observations

Hot on the heels of the MSI-high rectal cancer IO study update at the AGITG ASM in Christchurch in November last year, Andrea Cercek presented additional data. The cohort is now 42 patients, treated upfront with dostarlimab – all with complete clinical responses, all spared chemo, radiotherapy, and surgery. Patients are now going out on swimmer plots to 50 months. In support of our growing enthusiasm for ctDNA, in this study ctDNA was comparable, as sensitive, and acted as an earlier readout like direct biopsies in tracking complete responses compared to other clinical measures.

 

Upper GI research highlights

According to Associate Professor Amitesh Roy, Deputy Chair of the Upper GI Working Party and Study Chair for Neo-CREATE, a noteworthy theme at ASCO in upper GI research was biomarker-driven novel drug development, and the aim towards leveraging the immune system to produce meaningful benefit in difficult-to-treat upper GI malignancies.

“There were two phase I studies in early clinical development that caught my eye,” says Amitesh.

“One reported encouraging findings with use of novel autologous hypoxia-responsive CAR T-cell therapy targeting carcinoembryonic antigen (CEA) in GI malignancies. This study demonstrated antitumor activity and prolonged responses in patients with relapsed/refractory CEA-positive solid tumours, including gastric cancer and BTC.

“The other explored a GPC3-targeted CAR T-cell therapy armed to co-express a dominant-negative TGF-β receptor 2 (TGF-βR2), and produced a 50% response rate in heavily treated patients with advanced hepatocellular carcinoma.

“We will need to gear up to be able to do clinical trials with TIL and CAR-T cell therapies that will eventually change practice. This, along with several biomarker-targeted novel antibody drug conjugate (ADC) molecules (e.g., ADC targeting Claudin 18.2 in gastric cancer) is likely to change outcomes for patients with advanced upper GI malignancies.”

Amitesh’s trial to watch is the ESOPEC trial, which was presented in the plenary session.

“ESOPEC was a randomised, multicentre phase III trial that compared head-to-head two neoadjuvant strategies: CROSS vs (perioperative) FLOT in operable locally advanced oesophageal/ GOJ adenocarcinoma.

“Perioperative FLOT improved median OS by 29 months when compared with neoadjuvant CROSS, translating to a 30% reduction in the risk of death.

“In most patients, FLOT is likely be adopted as a more standard approach for oesophageal and GEJ cancers, although the option of CROSS, then surgery, then adjuvant nivolumab in select patients (less burden of disease and squamous cell cancers) is still a viable option. Outcomes from the currently awaited MATTERHORN and DANTE trials will inform/transform practice further.”

Image of Rob Ramsay in a speech bubble.

Rob’s observations

So many gems shone throughout the Meeting, including real progress with CAR-T cell therapies such as promising antigens, e.g., Claudins and hypoxia activation, improved and companion therapies with G12C and G12D targeting, application of ctDNA in tracking HPV +ve SSCs and pancreatic cancer, and whether PD-L1 expression levels (and how they are measured) are helpful in predicting IO responses/patient eligibility.

Building data shows that IO positively contributes to chemo-radiotherapy in patients with residual oesophageal/gastric junction tumours. The comparison of FLOT versus CROSS was reported with FLOT appearing to be superior. What happens with upfront IO in MSI-H and EBV positive cases will be very interesting in the context of CROSS.

Regarding upper GI surgery, Liang Kang presented the TaLaR RCT which explored TaTME verses lapTME for patients with rectal cancer, showing comparable PFS trajectories over 3 years.

 

Translational research highlights

Professor Rob Ramsay noted growing evidence for upfront immunotherapy at the Meeting this year.

“There has been a real reluctance to consider this because it might delay standard of care and perhaps make matters worse. The opposite seems to be case in where defective mismatch repair is concerned,” says Rob.

“What happens with upfront IO in MSI-H and EBV positive cases will be very interesting in the context of CROSS.”

According to Rob, there are a number of trials to watch for their translational research aspect.

“Although not a GI trial, the NADINA study on stage 3 macroscopic melanoma where checkpoint antibodies (Nivo plus Ipi) were employed in the neoadjuvant setting showed spectacular responses. It met its objectives early and showed that only 6 weeks of treatment was effective.

“This will very likely be the new standard of care, further encouraging neoadjuvant immunotherapy in other tumour streams and providing improved patient outcomes at multiple levels. The companion NEJM publication, led by Christian Blank, Australian of the Year Georgina Long, and Peter Mac’s Shahneen Sandhu was released simultaneously at ASCO 2024. These studies set a precedent for future trials and will influence pharmaceutical funding.”

A development to keep track of this year is upfront IO. “Upfront IO in upper GI cancer, particularly for squamous cell carcinomas, may prove to be game-changing.”

Image of Rob Ramsay in a speech bubble.

Rob’s observations

One trial that needs particular mention is a study that began before COVID-19 with some resistance and became de rigueur during COVID-19. Joseph Greer of MGH presented the REACH PC telehealth trial on the “comparative effectiveness trial of early palliative care delivered via telehealth versus in person among patients with advanced lung cancer”. Essentially, both forms of care are equivalent and effective. These are important data in support of our AGITG colleagues Craig Underhill and Narelle McPhee’s efforts to champion telehealth in other important areas of care of our patients with GI cancer.

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