EML4-ALK Variant 3a/b as a mechanism of osimertinib resistance in a patient with EGFR L858R positive NSCLC

In September 2019, a 74-year-old woman was introduced to our hospital because of persistent right chest pain. She had a history of smoking (50 pack-years) and had undergone surgery for right breast cancer at 40 years of age without recurrence. Chest computed tomography (CT) revealed a mass in the upper lobe of the right lung (Figure 1A). She underwent CT-guided lung biopsy and was diagnosed with lung adenocarcinoma stage IVB (cT4N2M1c) with multiple lung and bone metastases. Bone metastases were detected in the transverse processes of the thoracic spine on PET at diagnosis; however, the effect of treatment was difficult to assess on CT due to the nature of the lesion. Notably, no significant deterioration of bone lesions, including the same site, was confirmed during the disease course. Cycleave PCR revealed that the tumor had an Epidermal growth factor receptor (EGFR) L858R mutation (Figure 3A), and we initiated osimertinib (Figure 1A). The best overall response to osimertinib was stable disease, and this treatment was continued for 15 months. In December 2020, she experienced progressive disease, and an ultrasound-guided tissue core biopsy of the right supraclavicular lymph node was subsequently performed (Figure 1B: white arrow).