Developing translational research projects and pilot/feasibility studies to collect data for larger clinical trials is a necessary to meet the challenges we face with lack of funding for large projects.
Many of the clinical trials in the AGITG portfolio collect tissue and blood samples from their patients. These samples are used in translational research studies to seek biomarkers. That is, biological flags that may help to select those patients most likely to benefit from a treatment, or to spare particular patients from harmful treatment.
Thirty-one AGITG clinical trials collect or have collected tissue and blood from patients. More than 80% of these trials have led to translational research studies. Work is progressing on many of these studies. Proposals using these patient samples undergo scientific review by the trial management committees, the Upper and Lower GI Working Parties, and the Scientific Advisory Committee.
For example, the joint AGITG-Canadian Cancer Trials Group Correlative Research Committee reviews proposals relating to the GI trial collaborations between AGITG and the Canadian Clinical Trials Group, including CO.17, CO.20 and CO.23. The translational research collaborations are with a broad mix of clinical and scientific researchers from Australia, New Zealand and overseas.
Key highlights – translational research studies for 2016
- A blood biomarker study from the AGITG INTEGRATE trial was presented as a poster at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) in San Francisco by translational research fellow and manager, Dr Sonia Yip1. The study showed that high plasma levels of IL8, VEGF-A and sVEGFR-1 may be adverse prognostic factors in patients with refractory advanced oesophago-gastric cancer. Video presentations of the study were made for online education sites HemOnc Today and prIME Oncology. The study was included in an article on regorafenib treatment (an oral multi-kinase inhibitor) for GI cancers in the European Medical Journal2.
- A study of hypertension and betablocker use in patients with metastatic colorectal cancer in the CO.17 trial showed these factors are neither significant prognostic factors nor predictive of benefit from treatment with cetuximab, though patients with baseline hypertension may do better on cetuximab. This was presented in a poster at ASCO GI by Canadian collaborator Dr Shelly Sud, medical oncologist3.
- Two studies on the easily obtained and inexpensive blood biomarker, the neutrophil, to lymphocyte ratio (NLR), were presented as posters at the European Society for Medical Oncology 2016 Congress (ESMO 2016) by medical oncologist Dr Connie Diakos. One study was based on the metastatic colorectal cancer trials CO.17 and CO.204. It found that high derived NLR at baseline in patients was associated with poorer overall survival. Another study based on data from the AGITG MAX trial showed that NLR is an independent prognostic marker for both progression-free survival and overall survival in metastatic colorectal cancer patients receiving first line treatment 5.
- A study of gene mutation variations in CO.17 trial patient tissues was published in Clinical Cancer Research, showing that cetuximab worked best in patients with KRAS wild-type colorectal cancers carrying a specific gene polymorphism in the Fc-y receptor (FCGR2A H/H genotype) 6.