Combination therapy recommended for NHS use for biliary tract cancer 

Biliary tract

AstraZeneca has announced that the National Institute for Health and Care Excellence (NICE) has recommended Imfinzi (durvalumab) in combination with gemcitabine and cisplatin (chemotherapy) for NHS use in England and Wales for the first-line treatment of adults with locally advanced, unresectable, or metastatic biliary tract cancer (BTC).1

There remains a significant unmet need for new treatment options in BTC, a group of rare and aggressive cancers that occur in the bile ducts and gallbladder, with approximately only 5-15% of patients surviving five years.2,3,4 Worldwide, bile duct cancer, or biliary tract cancer as it is most commonly known, is the second most common primary liver cancer with incidence rates increasing in many western countries, including the UK.5,6

Dr Mairéad McNamara, Senior Lecturer at the University of Manchester and Honorary Consultant at the Christie NHS Foundation Trust in Manchester, UK, said: “Following the release of today’s decision by NICE, patients with locally advanced, unresectable, or metastatic biliary tract cancer (who have not received previous treatment for advanced disease), can discuss with their treating oncologists the possibility of accessing a new treatment option (durvalumab in addition to standard of care cisplatin and gemcitabine) that can help to improve outcomes. Results from the TOPAZ-1 trial showed that there were approximately twice as many patients with advanced biliary tract cancer alive at two years following receipt of durvalumab with cisplatin and gemcitabine versus cisplatin and gemcitabine combination alone.” 

Helen Morement, Founder and CEO, AMMF at the Cholangiocarcinoma Charity, UK, said: “We are delighted to welcome this decision today from NICE. Cholangiocarcinoma (bile duct cancer), one of the biliary tract cancers, presents many challenges as it can be very difficult to diagnose accurately and early. Most new cases are diagnosed at an advanced stage, and so this recommendation is a huge step forward for people affected who will now have a much-needed new first-line treatment option beyond standard of care chemotherapy alone.” 

Regulatory milestones for durvalumab

Durvalumab was granted an Innovation Passport in Great Britain based on this specific indication. This means durvalumab was granted intellectual property (IP) and included in the Innovative Licensing and Access Pathway (ILAP), which aims to reduce the time it takes innovative treatments to be made available to NHS patients.7,8

Results from the primary endpoint of the TOPAZ-1 Phase III trial showed that durvalumab, in combination with standard of care gemcitabine plus cisplatin (chemotherapy) demonstrated a clinically meaningful and durable overall survival (OS) benefit as a treatment for patients with advanced BTC.6 Initial data reported a median overall survival of 12.8 months in the durvalumab in combination with gemcitabine and cisplatin group compared to 11.5 months in the gemcitabine and cisplatin plus placebo group (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.66-0.97, p=0.021).9 

An additional 6.5 months of follow-up data, from the intention-to-treat (ITT) population with durvalumab plus gemcitabine and cisplatin, increased the median overall survival from 11.3 months to 12.9 months (HR 0.76; 95% CI 0.64-0.91, no p value) compared with gemcitabine and cisplatin plus placebo.6 More than double the number of patients were estimated to be alive at two years versus chemotherapy alone (23.6% versus 11.5%).10 

Tom Keith-Roach, President, AstraZeneca UK, said: “Today’s milestone approval is AstraZeneca’s first in GI cancers in England and Wales. This extremely welcome news supports our ambition to work with NHS partners to challenge treatment expectations for patients with limited treatment options. We are passionate, determined people, working with constructive impatience to make a difference for patients.” 

David Brocklehurst, Head of Oncology, AstraZeneca UK, said: “Today’s decision by NICE takes us one step closer to fulfilling our ambition to one day eliminate cancer as a cause of death. Under 15% of patients with biliary tract cancer live for five-years or more. The need for new treatment options is obvious. We hope that adding an innovative immunotherapy to the treatment options available will play an instrumental role in changing the course for patients.” 

Trial details

Durvalumab plus gemcitabine and cisplatin was generally well-tolerated in the TOPAZ-1 trial. Grade 3 or 4 treatment-related adverse events (AEs) were experienced by 60.9% of patients treated with durvalumab plus gemcitabine and cisplatin, and by 63.5% of patients receiving chemotherapy alone.6 Durvalumab plus gemcitabine and cisplatin did not increase the discontinuation rate due to AEs compared to chemotherapy alone (8.9% for the durvalumab combination versus 11.4% for chemotherapy).10 

The most common adverse events were anaemia (48.2%), nausea (40.2%), constipation (32.0%), and neutropenia (31.7%) in the durvalumab plus chemotherapy group and anaemia (44.7%), nausea (34.2%), and decreased neutrophil count (31.0%) in the placebo plus chemotherapy group.9

  1. National Institute for Health and Care Excellence. Final Draft Guidance. Durvalumab with gemcitabine and cisplatin for treating unresectable or advanced biliary tract cancer. Issue date: 23 November 2023. 
  2. Marcano-Bonilla L, et al. Biliary tract cancers: epidemiology, molecular pathogenesis and genetic risk associations. CCO. 2016;5(5) 
  3. ESMO. What is Biliary Tract Cancer. Available at: Last accessed: November 2023. 
  4. Turkes F, et al. Contemporary Tailored Oncology Treatment of Biliary Tract Cancers. Gastroenterol Res Pract. 2019;2019:7698786. 
  5. Khan SA et al. Rising Trends in Cholangiocarcinoma: is the ICD Classification system misleading us? J Hepatology. 2012;56; 848–854. 
  6. AMMF – The Cholangiocarcinoma Charity. Introduction to Cholangiocarcinoma. Available at: Last accessed: November 2023. 
  7. GOV.UK. Innovative Licensing and Access Pathway. Available at: Last accessed: November 2023. 
  8. GOV.UK. Press release: First Innovation Passport awarded to help support development and access to cutting-edge medicines. Available at: Last accessed: November 2023. 
  9. Oh D-Y, et al. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evidence. 2022;1(8). 
  10. Oh D-Y, et al. Updated overall survival from the Phase 3 TOPAZ-1 study of durvalumab or placebo plus gemcitabine and cisplatin in patients with advanced biliary tract cancer. Poster 56P. Presented at the 2022 ESMO Virtual Plenary Session, 16–18 March 2022. 

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