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.
A 42-year-old woman diagnosed with stage IV NSCLC (adenocarcinoma) was admitted to our hospital in August 2013 and given an AP regimen (pemetrexed 500 mg/m2 on day 1, cisplatin 75 mg/m2 on days 1 to 3, repeated every 3 weeks) as initial chemotherapy on August 2nd, 2013. She received folate, vitamin B12, and corticosteroids as recommended. Several days later, her EGFR genetic test results demonstrated an exon 19 mutation (L747-T751>P); thus, she started taking gefitinib (250 mg once daily) on August 15th. On August 23th, which was 21 days after AP chemotherapy and 8 days after gefitinib treatment, the patient suddenly developed a widespread eruption including acne-like rash on the face, erythema papules on the trunk and limbs, oral ulcer, and conjunctivitis ( and ), followed by a fever of 39°C. The rash gradually increased and aggravated, accompanied with blisters, pruritus, and ulceration. Twelve days after gefitinib treatment, the patient was hospitalized. Gefitinib was immediately stopped, and imipenem, amikacin, and fluconazole were administered intravenously as prophylaxis, and diphenhydramine and loratadine were given as an anti-allergy treatment. On the 13th day, the patient's condition deteriorated further with a fever of 42°C, fused mucocutaneous rash as well as diffuse vesicles and bullae ( and ), which coalesced and then sloughed, presenting a scalded appearance. A positive Nikolsky sign was present on her back and feet ( and ). After consulting dermatology doctors, the patient was diagnosed with TEN and transferred to the Dermatology Department at the Second Affiliated Hospital of Sun Yat-sen University for further treatment.\nRoutine laboratory testing showed a white blood cell (WBC) count of 6.26 × 109/L [reference value: (3.69-9.16) × 109/L], neutrophil (NEU) proportion of 73.1% (reference: 50%-70%), and C-reactive protein (CRP) level of 16.36 mg/L (reference: 0-8.2 mg/L); both the Mycoplasma pneumoniae IgM antibody and Mac strains were negative. No suspicious fungus was found in the oral swab examination, nor did bacteria grow in the skin secretion culture.\nImmunosuppressive treatment was started with 100 mg methylprednisolone (daily injection) for 9 days and intravenous immunoglobulin (20 g/day) for 5 days, followed by 10 g/day for 5 days, accompanied with imipenem and teicoplanin for anti-infection and other supportive treatment. This treatment led to a recurrence of the rash and the mucosal lesions, reepithelization of the denuded skin (), and improvement of the patient's general condition within 40 days. A chest computed tomography (CT) scan and brain magnetic resonance imaging (MRI) showed partial remission after treatment. The combination of AP and gefitinib was suspended; accordingly, the patient began treatment with icotinib (another EGFR-TKI made in China) after recovery, without exfoliative dermatitis or other similar toxicities. Stable disease was later achieved.