Existing and prospective immunotherapeutics for biliary tract cancer

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Published: 3 Jan 2017
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Prof Junji Furuse - Kyorin University Hospital Cancer Centre, Tokyo, Japan

Prof Furuse speaks with ecancertv at the Immuno-Oncology Hong Kong 2016 meeting about the prospects of treating biliary tract cancer beyond surgical resection.

He describes the differing global incidence of biliary tract cancer, and introduces trials of checkpoint inhibitory immunotherapy alongside chemotherapy for treating these tumours.

Biliary tract cancer is recognised as a rare cancer in Western countries but a very common disease in Asian countries including Japan. So new agents for biliary tract cancer are not popular - breast cancer, colorectal, lung cancer are very potentially leading cancers for the development of new agents but biliary tract cancer is not a target for new agents right now but a very important thing, I think. Actually 23,000 patients are diagnosed in Japan as biliary tract cancer a year in Japan and 18,000 people die from biliary tract cancer so a very poor prognosis and it is very important to establish a more effective treatment for those patients.

Currently surgical resection is a potential curative treatment option but more than half the patients are not candidates for surgery so chemotherapy plays a very important role in treatment for biliary tract cancer but very limited available agents for those cancers. Gem plus S-1 is the standard of care for unresectable biliary tract cancer and S-1 which is a new fluoropyrimidine, oral fluoropyrimidine, but only three medicines are available for biliary tract cancer.

Today the topic, immune checkpoint inhibitors, could be promising for biliary tract cancer but there is few data currently for biliary tract cancer. One prospective clinical trial was published last year by Dr Bang in the ECCO meeting; the study demonstrated around an 80% response rate and a long duration of response was observed in some patients. So an immune checkpoint inhibitor would be promising for biliary tract cancer.

Currently in Japan a phase I trial of nivolumab is under investigation for unresectable biliary cancer in two ways – monotherapy after progression on gem plus cisplatinum or standard care and the other is a combination of nivolumab and gem plus cisplatinum as first line is also under investigation. Anyway, it would be of value to investigate nivolumab, pembrolizumab, whatever immune checkpoint inhibitors for biliary cancer.

What would be the message for doctors who are treating patients right now? Is it to wait for more data to come through or should they be looking at how they’re treating patients right now?

Actually many patients with biliary tract cancer receive chemotherapy using gem plus cisplatinum or S-1 but not enough. So they want to get new agents but very few clinical trials so very few opportunities to get access to clinical trials in Japan and also Western countries and Asian countries.

When would these results begin to impact doctors in the clinic?

I want to demonstrate a possibility, potential development, of a PD-1 inhibitor, PD-L1 inhibitor and anti-CTLA4 inhibitor for biliary tract cancer. Some case reports published a very good response to immune checkpoint inhibitors right now. So pharmaceutical companies should be conducting clinical trials for biliary tract cancer and our investigators encourage them and conduct clinical trials by investigating initiation trials. It’s very important.

Could you expand on how the treatment affects the different types of these cancers?

Biliary tract cancer consists of some tumour sites intrahepatic, extrahepatic biliary duct and gall bladder cancer and [?? 6:15] cancer so it’s very heterogeneous. Probably the biological characteristics are very different from tumour sites so we have to more examine the background of those cancers and what kinds of patients would be suitable for immune checkpoint inhibitors.

Another thing, pharmaceutical companies recognise biliary tract cancer as a rare disease so they don’t want to conduct more clinical trials but investigators collaborate with Western doctors, Asian doctors and good communication and encourage pharmaceutical companies and we ourselves conduct the clinical trial as an international collaboration.