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.
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.