atezolizumab and other immune-stimulatory anti-cancer drugs: risk of severe cutaneous adverse reactions (SCARs)

Last edited 06/2021 and last reviewed 03/2022

Cases of severe cutaneous adverse reactions, including Stevens-Johnsons syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in patients treated with immune-stimulatory anti-cancer drugs, including atezolizumab. Advise patients to be vigilant for the signs of severe skin reactions and to seek urgent medical advice if they occur

Severe cutaneous adverse reactions (SCARs) were previously known to be potentially associated with the use of atezolizumab. Based on evidence from a recent analysis, SCARs are now considered to be an identified risk for atezolizumab

Atezolizumab (Tecentriq) is an immune-stimulatory drug indicated for cancers including those of the bladder, lung, and liver – see product information for full indications.

SCARs are a heterogeneous group of delayed hypersensitivity reactions. These events mainly consist of acute generalised exanthematous pustulosis (AGEP), Stevens-Johnsons syndrome (SJS), toxic epidermal necrolysis (TEN), and rug reaction with eosinophilia and systemic symptoms (DRESS) and can be potentially life-threatening, and lead to severe, potentially chronic sequelae.

SCARS and atezolizumab

• based on clinical trials and post-marketing data, the most frequently reported range of time to onset was within 1 month after the first dose of atezolizumab (37%; 38 cases). Where reported, atezolizumab treatment was withdrawn or interrupted in 58 cases and the dose was not changed in 16 cases
• incidence rates of SCARs, regardless of severity, from pooled atezolizumab monotherapy (n=3178) and combination therapy (n=4371) company-sponsored clinical studies was 0.7% and 0.6% respectively

• other products used for cancers in the same class as atezolizumab, including cemiplimab, ipilimumab, nivolumab, and pembrolizumab list SCARs (including SJS and TEN) as a possible side effects in the Summary of Product Characteristics (SmPC) with an associated warning and precautions
• avelumab and durvalumab are known to cause other immune-mediated skin adverse reactions
• as for the other immune-stimulatory anti-cancer drugs, patients should be monitored for the signs and symptoms of serious skin reactions and treatment withheld or discontinued according to the severity of the event as described in the SmPC for each product

Advice for healthcare professionals:

• severe cutaneous adverse reactions (SCARs), including cases of Stevens-Johnsons syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in patients treated with immune-stimulatory anti-cancer drugs including atezolizumab
• advise patients of the need to seek urgent medical assistance if severe skin reactions occur
• monitor patients for signs and symptoms of severe skin reactions and exclude other causes
• if a SCAR is suspected, treatment should be withheld, and patients referred to a specialist for diagnosis and treatment
• if SJS or TEN is confirmed, or for any grade 4 (life-threatening) SCAR, permanently discontinue treatment with the immune-stimulatory drug
• caution is recommended when considering the use of immune-stimulatory drugs associated with SCARs in patients with previous history of life-threatening SCAR with other immune-stimulatory anti-cancer drugs
• report suspected adverse drug reactions on a Yellow Card - all suspected adverse drug reactions to black triangle medicines should be reported

• contact your doctor straight away if you experience itching, skin blistering, peeling or sores, or ulcers in the mouth or in lining of nose, throat or genital area
• always read the leaflet that accompanies your medicines and talk to your doctor, nurse, or pharmacist if you are concerned about any side effects

Reference:

• MHRA (June 17th 2021). Atezolizumab (Tecentriq) and other immune-stimulatory anti-cancer drugs: risk of severe cutaneous adverse reactions (SCARs) Drug Safety Update volume 14, issue 11: June 2021: 2.