Improving treatment standards for rarer cancers

Research at The University of Manchester has helped grow the evidence base for biliary tract cancers and set international treatment standards that have improved survival rates.

Global challenge: understanding lesser researched cancers

Biliary tract cancers (BTC) comprise a number of different cancers that develop in the bile ducts of the liver and gallbladder.

They have a low incidence in high-income countries but a much higher rate in less affluent countries, including areas of Asia and India – with incidence levels rising. 

In such high-incidence areas, lack of health and research infrastructure and access to international research partnerships has meant that the disease has been poorly understood for decades.

Manchester solution: aiding clinical practice through collaboration

Our impact is being felt from curative treatment through to patients with advanced disease.

It’s improving overall survival for patients, their 
quality of life, and adopted into the international standard of care guidelines.  

Juan Valle / Professor in Medical Oncology

Researchers at The University of Manchester led the world’s first and largest randomised clinical trial - that a decade later - continues to be the standard in care in treating BTC.

Before this trial, the evidence base for BTC disease was low, research lead Professor Juan Valle explains: “We went for decades with very little evidence to base our practice on as the diseases were considered too rare to study.  

However, it became clear to us that the problem wasn’t as much to do with the rarity of the cancer, but the lack of collaboration, the collective research strength to produce meaningful outputs.” 

To help counter this, the team developed and led a UK collaboration, the Advanced Biliary Tract Cancer (ABC)-02 trial, demonstrating that these studies are possible in countries where the incidence is low.  

Game changers in treatment standards

The research trial demonstrated that cisplatin and gemcitabine improved the survival of patients with BTC. It became the standard treatment internationally and the comparator for all other treatments. Since 2010, nothing has been shown to be superior in other studies. 

After the trial, the team looked at how to treat patients with advanced disease when treatment with cisplatin and gemcitabine was no longer effective, Juan explains: “While we were able to provide level one trial evidence from randomised control trials to tell us how patients should be managed initially, the next area of need was in patients who either didn’t respond or initially responded to treatment and later developed disease progression.  

“It’s a poor-prognosis tumour, and while we’re quite a low incidence area in the UK, the incidence in the Far East is ten-fold higher, highlighting the global unmet medical need of these patients.” 

A further trial followed, called the ABC-06 study, which set another international standard of care for second-line chemotherapy, with FOLFOX chemotherapy (a combination of 5-fluorouracil and oxaliplatin).   

Professor Valle explains: “These two studies are the big game changers in patients with advanced disease, but we also delivered a study looking at potentially-cured patients after they had undergone surgery. It showed that giving a six-month course of chemotherapy post-surgery improves survival.  

“What we have delivered through these three studies are standards of care in the first- and second-line advanced settings as well as the standard of care after surgery, and are now firmly established in international guidelines and are the benchmarks for future studies.” 

The future of BTC treatment

The team are now looking at how cancer precision medicine can be applied to patients with BTC by identifying patients with different molecular subgroups where specific treatments can be offered.

Professor Valle added: “We are now looking for small sub-groups of patients with a rare cancer; this highlights the importance of international collaboration so that progress can be accelerated going forward.

“Our impact is being felt from curative treatment through to patients with advanced disease, it’s improving overall survival for patients, improving or maintaining their quality of life and the adoption into guidelines which are used as the international standard of care.

“We’re now in an era where we’re looking at patients from a precision medicine point of view."

Life-changing impacts

The University of Manchester’s research has: 

  • set the international standards of care which have been adopted into international guidelines;
  • helped reduce disease recurrence and improve overall survival for patients after surgery;
  • helped improve overall survival and maintain quality of life for patients with advanced disease.