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 III 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 reports of radiation injury and related events in patients receiving vemurafenib. Suspected adverse reactions to vemurafenib should be reported to us on a Yellow Card.
19 October 2015
Article citation: Drug Safety Update Vol 9 issue 4, November 2015: 2.
Published 12 November 2015