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.
In October 2017, a 51-year-old man, suffering from loose blisters, large-area skin peelings (nearly involving the entire body), mucosal erosion and fever, visited The First Affiliated Hospital with Nanjing Medical University. He had been diagnosed with stage IV EGFR-mutation-positive advanced NSCLC with pleural metastasis in 2016 and received treatments at a thoracic hospital regularly. After chemotherapy (pemetrexed plus cisplatin for six cycles) was completed, icotinib continued to be used till August 2017 when the drug resistance was revealed. Once EGFR T790M mutation was diagnosed, he started taking AZD-9291 with a dose of 80 mg/day to delay the disease progression. Twenty-one days later, he presented with several oral blisters and scattered erythematous maculopapular rashes, which rapidly developed into mucosal erosion and general epidermal detachment involving his entire body with exfoliation on his back skin (). When admitted into our department, he was unable to get up owing to severe pain, extreme feebleness, fever, and lower limb edema.