The theme at the 2023 ASCO Annual Meeting was ‘Partnering with Patients: The Cornerstone of Cancer Care and Research’.

Throughout the meeting, there were multiple talks focussed on quality of life and financial toxicity. These included presentations of the PROSPECT trial, a randomised phase III noninferiority trial for locally advanced rectal cancer, and the D-TORCH trial, a randomised study on the use of an over-the-counter treatment to prevent hand-foot syndrome (HFS) in patients with breast or GI cancer.

There was also a spotlight on electronic data collection of patient-reported outcomes (PROs). “We are delighted to be able to report toxicities not just as they were reported by physicians, but as they were reported by patients,” said Dr Deborah Schrag, who presented the PROSPECT study.

For the first time, the meeting also featured a session on the impact of microbiome on cancer outcomes.

Upper GI highlights

The following highlights include contributions by Dr Sarah Hayes, AGITG Translational Research Coordinator.

PALEO and ASCEND

Two AGITG trial posters were accepted at this year’s ASCO: the oesophageal cancer study PALEO, and the pancreatic cancer study ASCEND. This represents a growing recognition and global interest in the research led by AGITG members, as well as GI cancer research from Australia and New Zealand.

Notably, PALEO is a quality-of-life study which aims to alleviate symptoms of dysphagia in patients with oesophageal cancer, aligning with the theme of the meeting. Patients receive durvalumab concurrently with chemoradiotherapy to the primary oesophageal cancer, with stereotactic radiotherapy administered to a single metastasis.

The ASCEND trial aims to investigate the activity and safety of the addition of CEND-1/LSTA1 to standard of care chemotherapy with gemcitabine and nab-paclitaxel in patients with untreated metastatic pancreatic ductal adenocarcinoma.

The NORPACT-1 trial

Attracting much interest this year was the NORPACT-1 trial, which presented negative results. It compared short-course neoadjuvant FOLFIRINOX to upfront surgery in patients with resectable pancreatic head cancer. Surprisingly, the results demonstrated that short-course neoadjuvant FOLFIRINOX did not improve overall survival, with shorter survival in the neoadjuvant arm.

Interestingly, the study also showed that neoadjuvant mFOLFIRINOX did improve histological outcomes, although it did not improve survival.

The KEYNOTE-966 trial

The phase III KEYNOTE-966 trial presented a new option for unresectable locally advanced or metastatic biliary tract cancer. The study showed that adding pembrolizumab to gemcitabine and cisplatin improved overall survival by nearly two months, with equivalent health-related quality of life, compared to only gemcitabine and cisplatin.

As outcomes for advanced biliary tract cancer remain poor, adding immunotherapy without sacrificing quality of life presents another potential option for patient-centred care.

Lower GI highlights

The following highlights were contributed by Associate Professor Connie Diakos, medical oncologist and AGITG Scientific Advisory Committee Member.

The PROSPECT trial

Excitingly, a lower GI abstract made the plenary session this year. Dr Deborah Schrag presented the PROSPECT study, a randomised phase III trial examining neoadjuvant chemoradiation versus neoadjuvant FOLFOX chemotherapy with selective use of chemoradiation, followed by total mesorectal excision for the treatment of locally advanced rectal cancer. This was a non-inferiority study looking at intermediate risk patients. Of the patients in the FOLFOX group, 9% received neoadjuvant chemoradiation. FOLFOX with selective chemoradiation was non-inferior to chemoradiation for 5-year disease free survival (80.8% vs 78.6%, HR 0.92, P=0.0051), indicating there are a group of patients in whom pelvic RT can be omitted, sparing them from its associated toxicities.

Neoadjuvant treatment

Intensification of neoadjuvant treatment for patients with locally advanced rectal and colon cancer featured prominently, with a number of oral abstracts and posters presented.  The NeoCol study compared neoadjuvant chemotherapy to upfront surgery in patients with cT3 or cT4, cN0-2, M0 colon cancer, with no difference in disease-free or overall survival found. Downstaging was achieved, with less postoperative complications and less adjuvant chemotherapy required. The difficulty in identifying high-risk patients pre-operatively using CT staging however was noted.

Additional five- and seven-year updates were given for FOWARC and PRODIGE-23 respectively, examining total neoadjuvant therapy (TNT) for locally advanced rectal cancer. With longer follow-up, FOWARC found no significant difference in overall survival in patients who received neoadjuvant mFOLFOX6 chemotherapy, with or without radiotherapy, and no difference comparing mFOLFOX6 plus radiotherapy versus 5-FU plus radiotherapy. PRODIGE-23 found patients who underwent TNT with neoadjuvant mFOLFIRINOX in addition to chemoradiotherapy (CRT), surgery and adjuvant chemotherapy had significantly better outcomes to those who received standard CRT, surgery and adjuvant chemotherapy alone.

Translational research highlights

The following highlights include contributions by Dr Sarah Hayes and Associate Professor Connie Diakos.

Impact of microbiome on cancer outcomes

This year’s meeting brought the first-ever session focussing on the impact of microbiome on cancer outcomes. This is a welcome spotlight on the role of the GI system in cancer care, as well as of potential personalisation of care. Presentations at the session included the use of gut microbiome to predict response to immunotherapy and the transplantation of faecal microbiota combined with anti–PD-1 inhibitor for unresectable or metastatic solid cancers refractory to anti–PD-1 inhibitor.

Liquid biopsy and ctDNA analysis in trials

Another major focus on translational research at ASCO 2023 was the implementation of liquid biopsy and circulating tumour DNA analysis in clinical trials. Several oral abstracts and poster presentations highlighted the utility of these tools. In particular, the topic was highlighted in the early colorectal cancer research presented, including a case-based session in which Prof Jeanne Tie, Chair of the AGITG Lower GI Working Party, was featured.

Prof Tie is the Study Chair for the AGITG colorectal cancer trial DYNAMIC-III, which aims to utilise ctDNA analysis to inform treatment.

Photos: Dr Sarah Hayes