- Cabozantanib has been recommended by NICE for the treatment for HCC, in adults who have previously been treated with sorafenib,
- Results of the CELESTIAL phase 3 pivotal trial showed statistically significant improvement in progression free survival and overall survival compared with placebo
- Only 13% of people diagnosed with liver cancer in England survive for five years or more
SLOUGH, UK, 10 November 2022 – Ipsen UK today welcomed the decision from the National Institute for Health and Care Excellence (NICE) to recommend cabozantinib for treating hepatocellular carcinoma, a type of primary liver cancer, in adults who have previously been treated with sorafenib, only if they have Child Pugh grade A liver impairment and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. The recommendation is based on the results of the global placebo-controlled CELESTIAL phase 3 pivotal trial which included a patient population receiving cabozantinib in second or third line after treatment with sorafenib.
“People living with the most common form of primary liver cancer, HCC, have a poor prognosis and there are very few treatments available. Often, the disease is diagnosed so late that palliative care is the only option. The nurses on the British Liver Trust’s helpline hear every day from patients who are completely devastated. They live with uncertainty, hopelessness and often stigma and isolation due to the image of liver cancer. Treatments that buy extra time can not only positively impact those individuals but can also have a huge positive impact on families and the wider community, so today’s approval is an important step forward in the treatment of HCC.” said Vanessa Hebditch, Director of Communications & Policy, British Liver Trust
The trial met its primary endpoint of overall survival (OS), with cabozantinib providing a statistically significant improvement in OS compared with placebo in patients with advanced HCC who have been previously treated with sorafenib. The median OS in the overall population was 10.2 months with cabozantinib and 8.0 months with placebo (HR 0.76, 95 percent CI 0.63-0.92; p=0.0049). Corresponding to this survival benefit, a longer duration of progression-free survival was also observed: the median progression-free survival (PFS) was 5.2 months with cabozantinib and 1.9 months with placebo (HR 0.44, 95 percent CI 0.36-0.52; p<0.0001). Adverse events were consistent with the known safety profile of cabozantinib, and the rate of high-grade adverse events in the cabozantinib group was approximately twice that observed in the placebo group.
Professor Tim Mayer, Professor of Experimental Cancer Medicine at UCL Cancer Institute and Honorary Consultant in Medical Oncology at the Royal Free Hospital added, “HCC is the third leading cause of cancer death worldwide and has one of the lowest five-year survivals of all cancers. For patients with advanced disease, treatment options remain limited, and outcomes are poor. Today’s recommendation by NICE will make cabozantinib available to such patients and provides an important addition to the therapeutic landscape for HCC. Cabozantinib has been proven to improve survival, slow disease progression and delay deterioration in disease related symptoms when used as second- or third-line treatment, and the decision to allow its use will be welcomed by doctors treating this challenging disease.”
Manjinder Bains, Medical Director, Ipsen UK and Ireland comments, “We are pleased with the decision to make cabozantinib available to eligible liver cancer patients in England and Wales. At this stage of the disease, it is critical to intervene with another treatment that can prolong survival and delay progression, which we know can make such a difference to patients and their families living with this devastating condition. At Ipsen, we are committed to bringing innovative medicines to patients, and we continue to focus on addressing crucial areas of unmet need within our clinical trial programme.”
About CELESTIAL study
CELESTIAL is a randomised (2:1), double-blind, phase 3 trial of 707 patients with HCC. Patients were randomly assigned to receive cabozantinib (60 mg once daily) or matching placebo. Eligible patients had received previous treatment with sorafenib, had disease progression after at least one systemic treatment for hepatocellular carcinoma, and may have received up to two previous systemic regimens for advanced hepatocellular carcinoma. The primary end point was overall survival while the secondary end points were progression-free survival and the objective response rate.
Cabozantinib is an oral tyrosine kinase inhibitor administered daily with routine outpatient monitoring. Specifically, it inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellular carcinoma and the development of resistance to sorafenib, the standard initial treatment for advanced disease.
About hepatocellular carcinoma (HCC)
Hepatocellular carcinoma is the most common type of primary liver cancer in the UK. Most patients are diagnosed in the advanced stages of the disease, when cirrhosis is present and surgery is rarely an option, with the disease considered incurable. Without treatment, the median survival of advanced HCC ranges between 4 and 8 months. There are currently limited second and third line treatment options for people living with hepatocellular carcinoma.
Primary liver cancer is becoming more common at all ages. It is now the eighth most common cause of cancer death in the UK and has the largest increase in mortality over the past 10 years compared to all cancers. Only 13% of people diagnosed with liver cancer in England survive for five years or more.
Our team in the UK is a core part of Ipsen’s global biopharmaceutical business and is driven by the belief that patients don’t have time to wait. We have a biotech mindset coupled with pharmaceutical capabilities and have invested in a robust business presence in the UK that spans the early stages of R&D (Abingdon, Oxford) through to in-house manufacturing (Wrexham, Wales) so we can effectively deliver on our promise to UK patients. As part of this investment in the heart of UK life sciences, we employ over 700 people across our three major UK sites, including our commercial headquarters in Bath Road, Slough. For more information, visit ipsen.com/uk-ireland/
For further information:
 NICE. 2022. Cabometyx (cabozantinib) Final Appraisal Determination. Available from: https://www.nice.org.uk/. Last accessed: November 2022
 Abou-Alfa GK et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med. 2018 Jul 5;379(1):54-63
 Cancer Research UK. Liver cancer statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/liver-cancer. Last accessed November 2022
 Cancer Research UK. Types of Liver Cancer. Available at: https://www.cancerresearchuk.org/about-cancer/liver-cancer/types. Last accessed November 2022
 Park, J.W., et al., Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int, 2015. 35(9): p. 2155-66
 Cancer research UK. Survival. Available at: https://www.cancerresearchuk.org/about-cancer/liver-cancer/survival. Last accessed November 2022
 2nd Atlas of Variation in Risk Factors and Healthcare for Liver Disease in England 2017. Available at: https://fingertips.phe.org.uk/documents/7.LiverCancer.pdf. Last accessed November 2022