IMFINZI▼(DURVALUMAB) IN COMBINATION WITH GEMCITABINE AND CISPLATIN HAS BEEN ACCEPTED FOR USE IN SCOTLAND IN ADULTS WITH LOCALLY ADVANCED, UNRESECTABLE OR METASTATIC BILIARY TRACT CANCER

FOR IMMEDIATE RELEASE ON MONDAY 13 NOVEMBER AT 10:00

 IMFINZI▼(DURVALUMAB) IN COMBINATION WITH GEMCITABINE AND CISPLATIN HAS BEEN ACCEPTED FOR USE IN SCOTLAND IN ADULTS WITH LOCALLY ADVANCED, UNRESECTABLE OR METASTATIC BILIARY TRACT CANCER

 Imfinzi (durvalumab), an immunotherapy, has now been accepted for use by the Scottish Medicines Consortium (SMC) in combination with gemcitabine and cisplatin (chemotherapy), the latter of which has been standard of care for over a decade in this advanced biliary tract cancer population.[1]

• SMC acceptance is based on positive results from the TOPAZ-1 Phase III trial which showed that durvalumab in combination with gemcitabine and cisplatin more than doubled 2-year overall survival benefit in advanced biliary tract cancer (BTC) versus gemcitabine/cisplatin plus placebo (23.6% versus 11.5%), as well as reduced the risk of death by 24%.[2]
• BTC is a group of rare and aggressive cancers,[3]^,[4] with new cases often diagnosed at an advanced stage when the prognosis is poor.[5]^,[6]

London, UK, Monday 13 November 2023 – AstraZeneca today announced that the Scottish Medicines Consortium (SMC) has accepted Imfinzi (durvalumab) for use in combination with gemcitabine and cisplatin within NHS Scotland 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.^3,4,[7] Worldwide, bile tract cancer, or biliary duct cancer as it is most commonly known, is the second most common primary liver cancer with incidence rates increasing in many western countries.[8]^,[9]

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.[10]^,[11]

 Dr Arif Adnan Shaukat, Consultant Clinical Oncologist, Aberdeen Royal Infirmary said: “Durvalumab in combination with gemcitabine and cisplatin has shown to more than double overall survival at two years and reduce the risk of death by up to 24%. This recommendation from the SMC is an important milestone for patients in Scotland with locally advanced, unresectable, or metastatic biliary tract cancer who can now access a new combination treatment option that can help improve their outcomes.”

 Results from the primary endpoint of the TOPAZ-1 Phase III trial showed that durvalumab, in combination with standard-of-care chemotherapy (cisplatin and gemcitabine) demonstrated a clinically meaningful and durable overall survival (OS) benefit as a treatment for patients with advanced BTC.² Updated median OS was 12.9 months compared to 11.3 months with chemotherapy alone.² More than double the number of patients were estimated to be alive at two years versus chemotherapy alone (23.6% versus 11.5%).²

Helen Morement, Founder and CEO, AMMF – The Cholangiocarcinoma Charity, UK, said: “We are delighted to welcome this decision today from the SMC. 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 acceptance is a huge step forward for people affected in Scotland who will now have a much-needed new treatment option beyond chemotherapy standard of care.”

Tom Keith-Roach, President, AstraZeneca UK, said: “I am proud that we have been able to work with our partners in Scotland to ensure that people with this rare form of cancer have access to this new treatment.  We look forward to further collaborating with the SMC and NHS Scotland to ensure that more patients with harder to treat cancers can benefit from our innovations.”

 David Brocklehurst, Head of Oncology, AstraZeneca UK, said: “Until now, people with advanced biliary tract cancer have had very limited treatment options. Durvalumab is AstraZeneca’s first treatment for patients with GI cancers, adding to our growing portfolio of medicines that aim to revolutionise cancer care in the UK.  Durvalumab in combination with chemotherapy has shown a clinically meaningful overall survival benefit for these patients and we will now work with the Scottish NHS and clinicians to ensure that as many patients can benefit as possible.”

Data from TOPAZ-1 also showed enhanced clinical efficacy after an additional 6.5 months of follow-up for durvalumab plus cisplatin and gemcitabine (chemotherapy) demonstrating a 24% reduction in the risk of death versus chemotherapy alone [HR 0.76, 95% CI (0.64-0.91)].²

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 63% of patients treated with durvalumab plus gemcitabine and cisplatin and by 65% of patients receiving chemotherapy alone.¹ Durvalumab plus cisplatin and gemcitabine did not increase the discontinuation rate due to AEs compared to chemotherapy alone (8.9% for the durvalumab combination versus 11% for chemotherapy).¹

 The most common adverse events were anaemia (48.2%), nausea (40.2%), constipation (32.0%), and neutropenia (31.7%) in the durvalumab plus cisplatin and gemcitabine group and anaemia (44.7%), nausea (34.2%), and decreased neutrophil count (31.0%) in the placebo plus chemotherapy group.[12]

– ENDS –

CONTACTS

UK Media Enquiries

Emma White, AstraZeneca: 07385 516437 / emma.white1@astrazeneca.com

Jack Faulkner, Edelman: 07813 407324 / jack.faulkner@edelman.com 

NOTES TO EDITORS

About durvalumab

Durvalumab is a human monoclonal antibody that targets the programmed death ligand-1 (PD-L1), an important part of the mechanism that cancer cells use to hide from the body’s immune system. PD-L1 is expressed on T-cells and tumour cells. By selectively blocking PD-L1, durvalumab can enable the immune system to recognise and attack the cancer cell.[13]^,[14]

In February 2023, durvalumab was granted its marketing authorisation by the Medicines and Healthcare products Regulatory Agency (MHRA) under Project Orbis, an international programme coordinated by the US Food and Drug Administration (FDA), which provides a framework for the concurrent submission and review of oncology medicines among international partners.[15]  

For complete information on durvalumab, the summary of product characteristics, including a full list of side effects and adverse reactions is available here: https://www.medicines.org.uk/emc/product/9495/smpc

 About TOPAZ-1

TOPAZ-1 is a randomised, double-blind, placebo controlled, multicentre, global Phase III trial of Imfinzi (durvalumab) in combination with chemotherapy (gemcitabine plus cisplatin) versus placebo in combination with chemotherapy as a 1st-line treatment in 685 adult patients with unresectable, locally advanced, or metastatic BTC including intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer. Patients with ampullary carcinoma were excluded.[16]

The primary endpoint was overall survival and key secondary endpoints included progression-free survival, objective response rate and safety. The trial was conducted in 105 centres across 17 countries including in the US, Europe, South America, and several countries in Asia including South Korea, Thailand, Japan and China.16

 About biliary tract cancer

Biliary tract cancer (BTC) is a group of rare and aggressive gastrointestinal (GI) cancers that form in the cells of the bile ducts (cholangiocarcinoma), gallbladder or ampulla of Vater (where the bile duct and pancreatic duct connect to the small intestine).^3,4 Approximately 50,000 people in the US, Europe and Japan and about 210,000 people worldwide are diagnosed with BTC each year.[17]^,[18]^,[19] These patients have a poor prognosis, with approximately 5% to 15% of patients with BTC surviving five years.[20]

Cholangiocarcinoma is more common in China and Thailand and is on the rise in Western countries.^3,20 Gallbladder cancer is more common in certain regions of South America, India, and Japan.⁵

Early-stage BTC often presents with vague symptoms and therefore most new cases of BTC are diagnosed at an advanced stage, when treatment options are limited, and the prognosis is poor.^5,6

 AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its medicines are used by millions of patients worldwide.

With a proud 100-year heritage in advancing UK science, today AstraZeneca is the UK’s leading biopharmaceutical company. The company is based in five different locations across the UK, with its global headquarters in Cambridge. In the UK, around 8,700 employees work in research and development, manufacturing, supply, sales, and marketing. We supply around 36 different medicines to the NHS. 

For more information, please visit www.astrazeneca.co.uk and follow us on Twitter @AstraZenecaUK. 

References

[1] Scottish Medicine Consortium. Durvalumab concentrate for solution for infusion (Imfinzi^®): Detailed advice document SMC2582 – published 13 November 2023.

[2] 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.

[3] Marcano-Bonilla L, et al. Biliary tract cancers: epidemiology, molecular pathogenesis and genetic risk associations. CCO. 2016;5(5).

[4] ESMO. What is Biliary Tract Cancer. Available at: https://www.esmo.org/content/download/266801/5310983/1/EN-Biliary-Tract-Cancer-Guide-for-Patients.pdf. Last accessed: November 2023.

[5] Rawla P, et al. Epidemiology of gallbladder cancer. Clin Exp Hepatol. 2019;5(2):93-102.

[6] Banales JM, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nature Reviews Gastroenterology & Hepatology. 2020; 17: 557-588.

[7] Survival for bile duct cancer. Cancer Research UK. Available at: https://www.cancerresearchuk.org/about-cancer/bile-duct-cancer/survival. Last accessed: November 2023.

[8] Khan SA et al. Rising Trends in Cholangiocarcinoma: is the ICD Classification system misleading us? J Hepatology. 2012;56; 848–854.

[9] AMMF – The Cholangiocarcinoma Charity. Introduction to Cholangiocarcinoma. Available at: https://ammf.org.uk/cholangiocarcinoma/. Last accessed: November 2023.

[10] GOV.UK. Innovative Licensing and Access Pathway. Available at: https://www.gov.uk/guidance/innovative-licensing-and-access-pathway. Last accessed: November 2023.

[11] GOV.UK. Press release: First Innovation Passport awarded to help support development and access to cutting-edge medicines. Available at: https://www.gov.uk/government/news/first-innovation-passport-awarded-to-help-support-development-and-access-to-cutting-edge-medicines. Last accessed: November 2023.

[12] Oh D-Y, et al. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evidence. 2022;1(8).

[13] Stewart R, Morrow M, Hammond SA, et al. Identification and characterization of MEDI4736, an antagonistic anti–PD-L1 monoclonal antibody. Cancer Immunol Res. 2015;3:1052-1062.

[14] Patel S, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14:847-856.

[15] GOV.UK. Guidance on Project Orbis: what the Project Orbis initiative is and MHRA involvement in this regulatory path. Available from: https://www.gov.uk/guidance/guidance-on-project-orbis. Last accessed: November 2023.

[16] Clinicaltrials.gov. Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1). Available at: https://clinicaltrials.gov/ct2/show/NCT03875235. Last accessed: November 2023.

[17] Siegel RL. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7-30.

[18] ECIS - European Cancer Information System. Available at: https://ecis.jrc.ec.europa.eu/explorer.php. Last accessed: November 2023.

[19] Kohei Nakachi, et al. Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group, A randomized Phase III trial of adjuvant S-1 therapy vs. observation alone in resected biliary tract cancer. Japan Clinical Oncology Group Study (JCOG1202, ASCOT), Japanese Journal of Clinical Oncology. 2018,48:392-395

[20] Turkes F, et al. Contemporary Tailored Oncology Treatment of Biliary Tract Cancers. Gastroenterol Res Pract. 2019;2019:7698786.