INTEGRATE IIa results presented
Results for INTEGRATE IIa, a phase III AGITG trial, were presented at the 2023 ASCO Gastrointestinal Cancers Symposium. The trial evaluated regorafenib for the treatment of patients with advanced gastro-oesophageal cancer (AGOC) and met its primary endpoint of a statistically significant improvement in overall survival of about 30%.
The INTEGRATE IIa study is an international, double blind, placebo-controlled trial with 2:1 (regorafenib:placebo) randomisation of patients with evaluable gastro-oesophageal adenocarcinoma in the third line setting or later line.
It is currently followed by INTEGRATE IIb, an ongoing international randomised phase III trial in pre-treated patients with AGOC, comparing the combination of regorafenib and nivolumab to standard chemotherapy.
Lower GI highlights
The following highlights were contributed by A/Prof Jeanne Tie, Chair of the AGITG Lower GI Working Party.
The SUNLIGHT trial
The SUNLIGHT study is a randomised phase III study comparing the efficacy and safety of trifluridine/tipiracil (FTD/TPI) plus bevacizumab versus FTD/TPI alone in patients with refractory metastatic colorectal cancer.
The study met its primary endpoint of improvement in overall survival with a median 3.3 months survival gain in the FTD/TPI + bevacizumab arm (10.8 vs 7.5 months, HR 0.61, P<0.001). Survival benefit was observed across pre-specified subgroup including the 76% of patients who received prior anti-VEGF antibody. Progression-free survival was also longer in the experimental arm (5.6 vs 2.4 months, HR 0.44, P<0.001). Objective response rate was 6.3% vs 0.9% in each arm.
This study is practice changing and FTD/TPI plus bevacizumab should be the new standard of care treatment for refractory metastatic colorectal cancer.
Locally advanced rectal cancer
There were several oral and rapid oral abstracts as well as educational sessions on the management of locally advanced rectal cancer, from non-operative management (NOM) to intensifying total neoadjuvant therapy (TNT).
The OPERA trial investigated the use of radiation dose escalation with brachytherapy in addition to standard chemoradiation as NOM for cT2 to cT3a-b rectal cancer. This approach offers an excellent organ preservation rate of 79% at 3 years. Updated data from the NRG-GI002 (TNT) nested randomised phase II study was also presented.
This study enrolled very high-risk rectal cancer who received induction FOLFOX chemotherapy followed by chemoradiation with or without an experimental agent. Interestingly, an improvement in 3 year overall survival (95% vs 87%) but not DFS was observed with pembrolizumab in combination with chemoradiation compared to control. Further biomarker study (including MMR status) will be pursued.
Upper GI highlights
The SPOTLIGHT trial
The SPOTLIGHT trial is a randomised phase III study for gastric and gastro–oesophageal junction (GEJ) cancer, evaluating the efficacy, safety and tolerability of zolbetuximab in combination with mFOLFOX6, compared to placebo in combination with mFOLFOX6.
Zolbetuximab is an experimental drug, an investigational monoclonal antibody targeting the protein CLDN18.2, which is expressed on cancerous gastric epithelial cells. The study met its primary endpoint, finding that both progression-free survival and overall survival were significantly improved with zolbetuximab across most subgroups.
The statistically significant positive results mean that standard of care is likely to change with this study. “SPOTLIGHT establishes zolbetuximab in combination with mFOLFOX as an alternative new standard first-line treatment of advanced HER2-negative, CLDN18.2-positive gastric and GEJ cancer, especially in those who are not candidates for immunotherapy,” Dr David H. Wang, discussant, was quoted as saying.
Personalising treatment of upper GI cancers
There were a considerable number of abstracts involving the use of biomarkers or genomic sequencing to personalise upper GI cancer treatment, ranging from a study of the feasibility of preoperative circulating tumour DNA (ctDNA) in gastro–oesophageal cancer patients to proteomic profiling of antibody-drug conjugate (ADC) biomarkers in patients with pancreatic cancer.
One conference session focussed on pancreatic cancer biology. A Monash University study aimed to utilise pancreatic biopsies obtained via endoscopic ultrasound (EUS) for complete targeted DNA/RNA sequencing. Led by Dr Daniel Croagh and Dr Owen McKay, who are also leading the AGITG trial ACME ABC, molecular profiling was completed for 102 patients. The study confirmed EUS biopsies as “a valuable and reliable source of genetic material for clinically relevant molecular tumour profiling”.