- Initial treatment with chemotherapy only may be preferable to an immune checkpoint inhibitor (ICI)-based regimen in never-smokers with NSCLC, pending results of tissue-based next-generation sequencing to identify oncogenic driver.
- A new report describes a fatal skin immune-related adverse event (irAE) in a patient after switching from ICI treatment to osimertinib.
Why this matters
- Switching to a tyrosine kinase inhibitor (TKI) such as osimertinib after treatment with an ICI is uncommon and has been associated with severe irAEs, similar to those seen with concurrent TKI-immunotherapy treatment.
- A South Asian female never-smoker, aged 72 years, with stage IVB NSCLC, adenocarcinoma subtype.
- EGFR was wild-type on tissue and circulating tumor DNA, negative for ALK and ROS1, and PD-L1
- Patient received 2 cycles of chemotherapy (carboplatin and pemetrexed), followed by 2 cycles of chemotherapy plus pembrolizumab, with no irAEs.
- Genotyping revealed a rare EGFR exon 20 insertion, prompting a switch to osimertinib 3 weeks after the last chemo-immunotherapy treatment.
- 3 weeks after osimertinib initiation, the patient was admitted with diarrhea, severe stomatitis, and widespread maculopapular blanching rash.
- Osimertinib was discontinued; the patient received intravenous (IV) fluids, antibiotics, topical emollients, and hydrocortisone.
- Patient was diagnosed with toxic epidermal necrolysis after dermatoses spread to >90% of her body surface area and she developed epidermal necrolysis with a positive Nikolsky sign.
- After transfer to ICU, she received high-dose IV methylprednisolone, IV immunoglobulin, nasogastric-enteral feeding, and dressings.
- Skin biopsy showed an intense interface inflammatory infiltrate with basal vaculoar degeneration and formation of several apoptotic bodies.
- Patient died 19 days after admission.
- Single-patient case study.