- Medicines and Healthcare products Regulatory Agency
- 12 November 2015
- Therapeutic area:
- Cancer and Radiology and imaging
Prescribers should be aware of the risk of potentiation of radiation toxicity with vemurafenib when given before, during, or after radiotherapy
Advice for healthcare professionals:
- Vemurafenib should be used with caution when given before, during, or after radiotherapy and prescribers should be aware of the risk of potentiation of radiation toxicity
- Suspected adverse reactions to vemurafenib should be reported to us on a Yellow Card
Vemurafenib (Zelboraf▼) is indicated as monotherapy for the treatment of adults with BRAF V600 mutation-positive unresectable or metastatic melanoma.
A review of worldwide data by EU medicines regulators concluded that vemurafenib can potentiate radiation toxicity. In phase III1 and phase IV clinical trials, approximately 1 in 20 patients who received vemurafenib had a radiation-related injury, either radiation recall or radiation sensitisation (see below).
These cases occurred in patients who received radiation before, during, or after treatment with vemurafenib. Most cases were confined to the skin, but some involved visceral organs and resulted in a fatal outcome (including one case of radiation necrosis of the liver and two cases of radiation oesophagitis). Most patients had received doses of radiation ≥2 Gy/day.
Cases of radiation recall were confined to the previously irradiated area. Most cases (5 of 8) affected the skin, although 2 cases involved the lung and 1 case the bladder. Skin reactions included: eczematous, vesicular, or ulcerative lesions; erythema; and hyperkeratosis. Mean time to onset of radiation recall after vemurafenib initial dose was 12 days (range 7–21) for skin reactions, 24 days for pneumonitis; and 1 day for cystitis.
Most cases of radiation sensitisation (9 of 12) involved the skin, although there has been a case each involving the oesophagus, liver, and rectum. The nature of skin radiation sensitisation was similar to that seen in radiation recall skin reactions. Except for one case, vemurafenib was given concomitantly with radiation or within 3 days after completion of radiotherapy. When reported, the mean time to onset of the reaction after initiation of radiotherapy or vemurafenib was 10 days (range 3–27).
Up to October 2015, we have received 2 UK Yellow Card reports2 of radiation injury and related events in patients receiving vemurafenib. Suspected adverse reactions to vemurafenib should be reported to us on a Yellow Card.
See letter sent to healthcare professionals 19 October 2015
Article citation: Drug Safety Update Vol 9 issue 4, November 2015: 2.
Chapman PB and others, for the BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. New England Journal of Medicine 2011: volume 364, issue 26, pages 2507–2516 (viewed on 11 November 2015). Note that the study publication does not include radiation toxicity data; reference is included for information. ↩
Yellow Card reports are spontaneous reports of suspected adverse drug reactions (ADRs) submitted voluntarily by healthcare professionals and members of the public in the UK. The number of reports received should not be used to determine the incidence of an ADR. This is because neither the total number of ADRs occurring, nor the number of patients using the drug is known. ADR reporting rates are influenced by the seriousness of ADRs, their ease of recognition, and the extent of use of a particular drug, and may be stimulated by publicity about a drug. ↩
Published: 12 November 2015