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 68-year-old never-smoking female was referred to our outpatient clinic due to the stage IV lung adenocarcinoma, with involvement of the right supraclavicular lymph nodes and pelvic bones. Microscopic diagnosis was obtained via bronchoscopic biopsy and further confirmed by histologic examination of the tissue material form core needle biopsy of the supraclavicular node. The medical history included hypertension, ventricular extrasystoles, secondary hypothyroidism (after partial thyreoidectomy due to thyroid adenoma), degenerative spine disease and hypercholesterolemia. Cisplatin and pemetrexed were used as the 1st line treatment (from December 2010 to March 2011). Due to progression of the lesion in the right lung, the patient received four cycles of docetaxel (from July 2012 to September 2012) and, subsequently, the palliative radiation to the chest in February 2013.\nIn July 2013, the patient was diagnosed with liver metastases. The liver lesion biopsy revealed activating EGFR mutation (exon 19 deletion), and the patient was enrolled in the clinical trial OAM4971G, comparing combination of erlotinib and onartuzumab (monoclonal antibody blocking MET protein signalling) with erlotinib treatment only. During the study the patient developed facial rush (grade 1), recognized as associated with erlotinib treatment. In the chest and abdomen CT (September 2013 and November 2013) tumour partial regression was reported. There were no clinically significant abnormalities in laboratory testing.\nIn March 2014 the patient was informed about negative outcome of the clinical trial. Unblinding revealed that the patient was treated in placebo/erlotinib arm, and, therefore continuation of erlotinib 150 mg QD was offered. The patient did not report any further toxicity until April 2015, when G2 paronychia appeared. The skin changes were located around nail folds, mostly of left hand fingers, and required the use of amoxicillin with clavulanic acid.\nIn July 2015, after 24 months of erlotinib treatment, the progression of liver metastases was diagnosed. The patient was proposed 3rd line chemotherapy, i.e. paclitaxel 80 mg/m2 weekly over 3 week-period and 1 week-break thereafter. The treatment resulted in partial response that was maintained until April 2016. Because of availability of osimertinib within extended access programme, liver metastasis biopsy was performed, resulting in confirmation of T790M resistance mutation by Cobas test. In the abdomen CT (December 2016), further progression of liver metastatic lesions was confirmed, with lesions’ dimensions of 60 x 67 mm and 24 x 36 mm, respectively.\nIn December 2016 the patient began treatment with osimertinib 80 mg QD. In the first follow-up abdomen CT after 8 weeks significant regression of liver metastasis was seen, with reduction of the sum of lesion dimensions by 48%. Currently, after 8 months of treatment the patient is not reporting any side effects. On the last imaging (July 2017) almost complete remission of the liver lesions and full control of the other foci was confirmed, after more than 6 years from the initial diagnosis of the metastatic lung cancer.