An 80-year-old woman with adenocarcinoma (cT4N0M1c [BRA, PUL], stage VIB) and harboring an EGFR-sensitizing mutation (L858R) was treated with osimertinib in December 2018 as the first-line treatment, which led to a partial response with marked tumor shrinkage, which was assessed by chest computed tomography after 3 weeks of osimertinib treatment in January 2019. Erythematous papules were observed on the anterior chest wall 32 days after osimertinib induction. Therefore, the patient was referred to the department of dermatology of our institution. Since the dermatologic adverse event (AE) was diagnosed as mild at that time, a topical corticosteroid ointment was prescribed without cessation of osimertinib treatment. However, diffuse erythematous rash rapidly spread over the patient’s trunk (A) and was accompanied by vesicles and purpuric macules; furthermore, targetoid erythema developed on her face (B) after 14 days. Therefore, osimertinib was immediately discontinued. However, the erythema and macules did not alleviate after osimertinib discontinuation and oral prednisolone at a dose of 30 mg was initiated 5 days after osimertinib discontinuation. Four days after the initiation of prednisolone, diffuse erythema with Nikolsky’s sign, general epidermal detachment, erosion and loose blisters developed over her entire body including the face (C). Based on these symptoms, a clinical diagnosis of TEN was made, which was supported by a skin biopsy showing acute interface dermatitis with eosinophil infiltration (D). Therefore, intravenous immunoglobulin (IVIG; 15 g/day) was immediately administered for 4 days. Ten days after IVIG treatment, the erythematous rash on the patient’s trunk disappeared and some scar lesions remained (A). Furthermore, general epidermal detachment, erosion and loose blisters on her face ameliorated with epithelialization (B). Therefore, oral prednisolone was gradually tapered off.
A 63-year-old male (an ex-smoker that quit 20 years ago, with smoking history of 15 pack-years) was referred to our outpatient clinic with NSCLC diagnosis to assess treatment options. The tumour was located in the right lung and spread to the mediastinal and supraclavicular lymph nodes. The lesion was detected in the chest CT (April, 2015) performed due to recurring mild exertional dyspnoea, decrease in exercise tolerance and dry paroxysmal cough. On histopathological examination of mediastinal lymph nodes biopsy obtained at mediastinoscopy and the right supraclavicular lymph nodes from fine-needle biopsy metastatic lung adenocarcinoma (TTF1+, Napsin A+) was diagnosed (June, 2015). The patient denied any weight loss. His medical history included mild prostatic hyperplasia, past lithotripsy due to urolithiasis, and in his youth hepatitis A. He is a farm worker.\nThe results of laboratory testing were within normal limits. The chest CT revealed suspicious additional changes in the lung parenchyma as well as bone lesions suggestive of metastases. In PET scan distant metastases were ruled out, however, due to significant regional spread of tumour (stage IIIB) the patient was not eligible for radical radiotherapy. In parallel to the staging procedures, the status of EGFR activating mutations was assessed and the exon 19 deletion was detected. The patient was therefore started on afatinib 40 mg QD.\nAfter 4 weeks of treatment the patient presentedwith a facial rash (grade 1). After 12 weeks of treatment diarrhoea ensued, however, the patient remained professionally active. Diet modification and loperamide as needed were advised. In the chest CT performed after 12 weeks of treatment there was a partial tumour response. With no laboratory abnormalities, the patient continued therapy for 12 months. The rash with no need of treatment persisted.\nIn August 2016 the patient experienced a pathological vertebral fracture with no evidence of lung cancer progression on chest imaging and no evidence of disease progression in the brain MRI. However, a few days later there appeared progressive paraparesis. The spine MRI revealed metastases in vertebral bodies of Th1, Th7 and Th8 with protrusion into the epidural space and spinal cord compression. The patient underwent neurosurgery (posterior decompression and C4-Th11 stabilisation), rehabilitation (physiotherapy and kinesitherapy) and palliative radiotherapy (30 Gy in 10 fractions) for affected area. The treatment with afatinib was continued.\nIn December 2016 (15th month of afatinib treatment) the chest CT revealed progression of the disease in the lungs. Genetic examination of circulating free DNA (cfDNA) was performed and EGFR T790M mutation was found. In December 2016 the treatment with osimertinib 80 mg QD was initiated. The severity of the neurological deficits was slowly improving and the patient recovered the ability to move his legs. Follow-up chest CT, performed after 2 months of treatment, revealed partial regression. In the following examination further regression was observed, with the sum of measurable dimensions of the lesions reduced in size by 38%. Currently, the patient is still experiencing a clinical benefit after 8 months of osimertinib treatment.