July 8, 2019 • 5 Min

Pancreatic Cancer Patients in the UK Benefit From Unique Precision Medicine Project

Dr. David Chang

Wolfson Wohl Cancer Research Centre Opening Day

Nationalized healthcare, often criticized for long waiting lists and limited resources, among other things, also presents some unique opportunities, and pancreatic cancer patients in the United Kingdom are reaping the benefits of their nationalized service.

Thanks to the Precision-Panc initiative, the 10,000 pancreatic cancer patients diagnosed annually in England, Scotland, Wales, and Northern Ireland are receiving some truly cutting-edge care, with many matched to clinical trials testing new therapies.

Launched in 2017 with majority funding from Cancer Research UK (CRUK), the UK-wide consortium of doctors and researchers makes the most of genomics to both treat pancreatic cancer and advance the understanding of the disease.

Started in Glasgow, Cambridge, Manchester, London, and Oxford, the network now extends to 20 treatment sites, and continues to grow. It also benefits from a direct link to the National Health Service (NHS); the healthcare system’s centralized infrastructure, records system, and nationwide network of doctors makes it much easier for Precision Panc to identify, recruit, and follow patients.

Collaboration and Clinical Trials

One of the best things about the consortium is its collaboration, says David Chang, a Reader (Associate Professor) in Surgery at University of Glasgow’s Wolfson Wohl Cancer Research Centre, and a leader of the Precision-Panc program. Because they are not in competition for paying patients, hospitals and research centers are more likely to work together, drawing on their individual strengths to provide a more complete and efficient service to all, he explains.

Within the Precision-Panc network, for instance, one research center is well known for its patient-derived tumor mouse models, while another has a very good radiotherapy program. “It’s all about bringing the right people, with the right skills, together,” Chang adds.

This also means the centers can create complementary clinical trial portfolios, eliminating duplication and maximizing the options available to patients. This has resulted in speedier and more flexible trials as well. And the consortium is extremely attractive to pharmaceutical companies, who like the convenience of being able to approach one broad body for access to the UK clinical trials network. That, in turn, leads to patient access to all the latest drugs.

Another benefit when designing clinical trials is the size of the UK. Because it is relatively small, it is possible to get a bird’s-eye view of the pancreatic cancer patient population profile.

“This means we know which ‘segments’ of clinical stage, performance status, and even the molecular segment of the population are being well-served in the clinical trial space, and where there may be opportunities to serve other segments of patients better, which means we can rationalize trial design to create a complementary, and non-competing precision oncology therapeutic development eco-system” Chang says.

The consortium is inclusive, and invites input from the whole UK pancreatic cancer research community. The Precision-Panc Therapy Testing Board meets four times a year to hear from anyone with a clinical trial concept. Chang notes that this sometimes leads to further collaboration. During one meeting, for example, a team presented promising research that was nearly ready for testing. One of the consortium members offered to help the scientists complete their data collection using the member’s facilities and expertise. The team will be returning to the board’s next meeting to present the results and discuss how to translate that into a trial as a next step.

One-Stop Shop for Precision Medicine

So how does Precision-Panc work for patients?

Any patient in the NHS who is suspected of having pancreatic cancer is referred to the program. They are asked if they would like to participate in genomic testing, which is done using a custom-made Next Generation Sequencing panel at Glasgow Precision Oncology Laboratory.

A patient seen by one of five specialists at Glasgow Royal Infirmary might have their tumor biopsied during a Wednesday clinic—ideally using an endoscopic ultrasound, as they are easier to slot in quickly—and sent to pathology, where the pathology test would be fast-tracked. Specialists could know the results by Friday, and patients could be seen by early the following week to be fully registered to Precision-Panc, after an explanation of the implication of tumor molecular profiling. The patient would see an oncologist soon after that to receive treatment, with the whole process taking about two weeks—quicker than it usually takes to get a preliminary CT scan.

During this process, the patient’s results are entered into the Precision-Panc data portal, which flags any relevant trials going on across the UK. It might mean a patient with a certain mutation or biomarker could skip traditional first-line treatments and start directly on a biomarker-selected trial.

Patients actually have multiple chances to participate in trials. Some might participate in several as their cancer changes, or when new opportunities arise. Their tumors would be re-biopsied each time, to provide a record of the cancer’s evolution, which may potentially inform treatment.

Precision-Panc currently has several of its own initiated trials. Dubbed PRIMUS (Pancreatic canceR Individualised Multi-arm Umbrella Study), they address different biological questions, at different stages of disease.

PRIMUS-001, for example, is a phase II study looking at two different chemotherapy regimens, FOLFOX-A (FOLFOX and nab-paclitaxel) and AG (nab-paclitaxel and gemcitabine) in patients with metastatic pancreatic cancer, to see whether response can be predicted with certain biomarkers. PRIMUS-002 is examining neo-adjuvant regimens of FOLFOX-A and AG in resectable and borderline resectable Pancreatic Ductal AdenoCarcinoma (PDAC), focusing on biomarker and liquid biopsy development. And PRIMUS-004 will be a multi-arm umbrella trial of biomarker-directed novel second-line treatments in metastatic pancreatic cancer, the first arm of which is testing whether a combination of PARP and ATR inhibitors might overcome platinum resistance.

Patient tumor samples are also used in both fundamental and translational research to improve the outcome of future patients as well as current ones. Areas of research include: defining the genetic characteristics of pancreatic cancer, developing biomarkers of prognosis and response to treatment, and understanding why some cancers are resistant to drugs, in order to develop new treatments.

“The Precision-Panc platform allows us to study the disease at the same time as testing our clinical trial hypotheses. It also offers patients with pancreatic cancer attractive trial options with novel therapies,” Chang says. “Our national team of clinicians, researchers, bioinformaticians, and lab staff all work with one thing in mind: improving patient outcomes.”