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First-of-a-kind once daily pill given regulatory green light for patients with rare type of skin cancer, UK

Patients with advanced basal cell carcinoma who are not suitable for surgery or radiotherapy, could benefit from Erivedge (vismodegib) which is available following conditional EMA authorisation for use in the UK and listing on the national Cancer Drugs Fund (CDF).*[1],[2]

Basal cell carcinoma (BCC) is the most common form of skin cancer in the UK[3],[4] and is often found on the head and neck.[5-12] Should it become advanced, by spreading to other sites (metastatic BCC), left to become large, or because of recurrence after treatment, it may become disfiguring and become inappropriate for standard treatments – surgery or radiotherapy (locally advanced BCCi).[5],[13]

Vismodegib, the first-of-a-kind once daily treatment, has been shown to shrink visible lesions (a cancerous change in tissue) in 47% of patients with locally advanced BCC inappropriate for surgery or radiotherapy (laBCCi) and shrink tumours in 33% of those with metastatic BCC (mBCC).[1],[14]

The advanced form of the disease affects up to 700 people a year in the UK,[15] so this is a welcome advance and a potential new treatment option for patients with laBCCi and symptomatic mBCC.1,13 Specialist clinicians in England will be able to apply for vismodegib via the CDF which has added the drug and criteria for funding to its nationally approved list.[2]

Dr John Lear, Consultant Dermatologist, Salford Royal NHS Foundation Trust said: “Advanced basal cell carcinoma can be a socially isolating and highly disfiguring disease that may impair patients’ facial structures and senses. Until now, there haven’t been any active treatment options available for patients for whom surgery or radiotherapy was not appropriate. Vismodegib, which has been shown to shrink tumours, is a welcomed new treatment option for patients with advanced BCC and should provide them with a promising new outlook.”

Vismodegib works by blocking the abnormal hedgehog cell signalling pathway.[16] Abnormal activation of this pathway is responsible for cell growth[17] and tumour development[16] in more than 90% of all BCC cases.[18] This was identified through work by Professor Phil Ingham and Cancer Research UK.[19]

Dr Harpal Kumar, Chief Executive of Cancer Research UK, said: “We are proud to have played a key role in the early development of this drug and we’re delighted that it has passed this regulatory hurdle and is approved for use in the UK. This drug is a major advance for the treatment of this disease, providing advanced basal cell carcinoma patients with a new treatment option. This is great news for patients and it’s thanks to the generosity of our supporters that we can invest in crucial early research which sparks advances like this.”

The ERIVANCE study investigated and showed that the median duration of progression-free survival for patients with laBCCi was 9.5 months when they were treated with vismodegib.[14] The most common drug-related adverse events were muscle spasms, hair loss, altered taste sensation, weight loss, fatigue, nausea, decreased appetite and diarrhoea.[1],[6] In addition, vismodegib may cause embryo-foetal death or severe birth defects therefore vismodegib must not be given to a pregnant woman.[1]

About advanced basal cell carcinoma

BCC is the most common skin cancer in the UK and the world[3],[4] and while for the majority of patients BCC lesions can be easily treated by surgery,[5],[13] in some patients (estimated at up to 700 patients in the UK)[15] the disease progresses and becomes advanced. Where the disease becomes large or recurrent it can become inappropriate for surgery and radiotherapy (laBCCi)[13] and may threaten key sensory organs such as the eye, ear or nose, as well as invading bone, muscles or nerves beneath the skin.[5],[13],[16]

About vismodegib

Vismodegib is indicated for the treatment of adults with locally advanced BCC that is inappropriate for surgery or radiotherapy and symptomatic metastatic BCC.[1] Vismodegib targets the underlying molecular driver of BCC.[16],[17] Abnormal signalling in a cell growth pathway, known as the hedgehog pathway, is implicated in more than 90% of BCC cases and vismodegib is designed to selectively inhibit abnormal signalling in the hedgehog signalling pathway.[16-18]

For further information please see the Summary of Product Characteristics (SmPC) here: http://www.medicines.org.uk/emc/ [1]

Source

1. Erivedge SmPC available at http://www.medicines.org.uk/emc
2. Cancer Drugs Fund. Available from: http://www.england.nhs.uk/ourwork/cdf/ [Last accessed: July 2013]
3. Cancer Research UK: Basal cell carcinoma. Available from: cancerresearchuk.org – types-of-skin-cancer#basal [Last accessed: July 2013]
4. Macmillan Cancer Support. Types of skin cancer 2013. macmillan.org.uk – Typesofskincancer.aspx [Last accessed July 2013]
5. Walling HW et al. Aggressive basal cell carcinoma: Presentation, pathogenesis and management. Cancer and Metastasis Reviews. 2003;23:389-402
6. Gallagher RP et al. Sunlight exposure, pigmentary factors and risk of nonmelanocytic skin cancer. I. Basal cell carcinoma. Arch Dematol 1995;131:157-63
7. Rubin AI, Chen EH et al. Basal-cell carcinoma. The New England Journal of Medicine. 2005;353:2262–9
8. Weiss GJ, Korn RL ‘Metastatic basal cell carcinoma in the era of hedgehog signaling pathway inhibitors’. Cancer 2012
9. Ting PT et al. Metastatic Basal Cell Carcinoma: Report of Two Cases and Literature Review. J Cutan Med Surg. 2005;9:10-15
10. von Domarus H, Stevens PJ Metastatic basal cell carcinoma: Report of five cases and review of 170 cases in the literature Am Acad Dematol. 1984;10:1043-1060
11. Lo JS et al Metastatic basal cell carcinoma: Report of twelve cases with a review of the literature J Am Acad Dematol 1991;24:715-719
12. Wong CSM et al. Basal cell carcinoma, clinical review. British Medical Journal. 2003;327:794
13. Von Hoff MD et al. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. The New England Journal of Medicine. 2009;361:1164-1172
14. Sekulic A, Midgen MR, Oro AE, et al. Efficacy and safety of vismodegib in patietns with advanced basal cell carcinoma (BCC): 12-month update of the ERIVANCE BCC study. Poster 1112PD presented at the European Society for Medical Oncology Congress, Vienna, Austria, September 28-October 2, 2012.
15. Roche. Data on File RXUKDONF00213, June 2012
16. Sekulic A, Migden MR, Oro AE et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Eng J Med. 2012;366:2171-2179
17. Scales SJ, de Sauvage FJ. Trends Pharmacol Sci. 2009;30:303-312
18. Epstein EH. Basal cell carinomas: attack of the hedgehog. Nat Rev Cancer. 2008;8:743-754
19. Cancer Research UK. Hedgehogs, flies and skin cancer – the story of vismodegib [online] 2012. Available from: scienceblog.cancerresearchuk.org – high-impact-science-hedgehogs-flies-and-skin-cancer-the-story-of-vismodegib/ [Last accessed: July 2013]

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