In clinical studies, patients using ingenol mebutate gel had a higher incidence of benign and malignant skin tumours than those using vehicle-only gel or a different actinic keratosis treatment. An in-depth European safety review of the drug is now underway.
Further informationView ingenol mebutate drug record
Healthcare professionals should advise patients using ingenol mebutate to be vigilant for changes to the treatment area and immediately seek medical advice if any new scaly red patches, open sores, or elevated or warty growths occur.
Ingenol mebutate should be used with caution in patients with a history of skin cancer.
Squamous cell carcinoma
The potential for ingenol mebutate to induce skin cancer was considered during the drug's initial licence application, based on the purported mechanism of action and findings from an animal study. Overall, the potential for tumour promotion was considered low but the manufacturer was asked to carry out a 3-year safety study to assess the risk of skin cancer, including squamous cell carcinoma.
The preliminary results of this study showed an increased incidence of squamous cell carcinoma with ingenol mebutate versus imiquimod cream.
In addition, a meta-analysis of 4 studies of the related compound ingenol disoxate (a non-licensed treatment investigated for actinic keratosis) showed a statistically significant increase in skin cancer at 14 months in the active treatment group compared with the vehicle gel group when analysing the incidence of all tumour types together, including basal cell carcinoma, Bowen’s disease, and squamous cell carcinoma.
The product information for Picato was previously updated as a result of data from a phase II trial showing an excess of keratoacanthoma in patients treated with ingenol mebutate gel compared with those those who received vehicle-only gel.
Other studies have not shown an increased incidence of skin tumours with ingenol mebutate.
In the past year, approximately 32,450 packs of ingenol mebutate gel were dispensed in the UK. From 2013 to August 2019, the MHRA received reports of 9 cases of skin malignancies in the UK associated with ingenol mebutate, including cutaneous squamous cell carcinoma (of which 1 was metastatic), atypical fibroxanthoma, neuroendocrine carcinoma of the skin, Bowen’s disease, and basosquamous carcinoma.