2024-01-16 16:52:31
A case reported in a woman treated for lung cancer.
The National Agency for the Safety of Medicines and Health Products (ANSM) warns of the risk of adverse skin events that may occur in patients treated with adagrasib [1, 2].
In France, this medicine (ADAGRASIB MIRATI THERAPEUTICS 200 mg tablet) is currently only available as part of a compassionate access program and clinical trials, in the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) with KRAS G12C mutation, following at least one line of prior treatment. A conditional European marketing authorization (AMM) has been granted to this new active ingredient in November 2023 under the name KRAZATI 200 mg tablet.
A fatal case of epidermal necrolysis in a French patient
The ANSM reports a case of fatal toxic epidermal necrolysis (Lyell syndrome) occurring in a 67-year-old woman treated with adagrasib on a compassionate basis for NSCLC with the following characteristics:
- patient previously treated with pembrolizumab;
- occurrence of an ascending maculopapular rash, initially on the lower limbs, 15 days following the start of treatment with adagrasib;
- affected 45 to 50% of the body surface, then up to 90%, with involvement of the oral, vaginal mucous membranes and conjunctiva: the skin biopsy was found to be compatible with Lyell syndrome;
- regarding four days later, bronchial congestion and deterioration of his respiratory condition;
- death from toxic epidermal necrolysis with multiple organ dysfunction syndrome approximately 2 weeks later;
- other medications taken by the patient: amoxicillin stopped 3 weeks before the onset of the clinical picture, pravastatin started 15 days before to replace atorvastatin.
Four additional cases of serious skin reactions and one non-serious case of skin toxicity were reported in patients receiving adagrasib alone or in combination.
To date, a causal link between the occurrence of toxic epidermal necrolysis and adagrasib cannot be excluded.
Following this fatal event, treatment initiations with adagrasib are suspended.
Additional investigations are underway to evaluate this signal and take appropriate measures.
What to do in the event of a skin reaction to adagrasib
Any sign of skin toxicity in patients taking adagrasib should lead to medical consultation:
- generalized skin pain;
- rash that spreads quickly;
- skin blisters and/or large areas of peeling skin;
- inflammation and then hemorrhagic erosions on the mucous membranes, including the mouth, nose, eyes, anus and genital areas.
Taking adagrasib should be stopped immediately. in case of suspicion Stevens-Johnson syndrome (SJS) or Lyell syndrome or bullous lesions. The patient should be referred to urgently to a dermatologist.
Treatment should be permanently stopped if the diagnosis of SJS or Lyell’s is confirmed.
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