INTRODUCTION: AZD9291 (osimertinib) is designed for acquired T790M mutation 
after first- and second-generation EGFR) tyrosine kinase inhibitors have been 
used. Some of the resistance mechanisms that present after osimertinib 
treatment, including a newly acquired EGFR C797S mutation, have been identified. 
It is unclear, however, whether the bypass pathway is also a mechanism of 
resistance in patients after osimertinib treatment.
METHODS: Cells from malignant pleural effusion were collected and cultured at 
the time of progression in a patient being treated with osimertinib. Tumor 
genotyping was done by matrix-assisted laser desorption ionization-time of 
flight mass spectrometry. EGFR, AKT, MEK, and ERK phosphorylation were 
determined. An anchorage-dependent colony formation assay was used for drug 
sensitivity.
RESULTS: An acquired mutation, BRAF V600E, was found in the patient at the time 
of progression while being treated with osimertinib. Cells grown from malignant 
pleural effusion were sensitive to BRAF V600E inhibitor and were more vulnerable 
to a combination treatment with osimertinib.
CONCLUSIONS: A potential mechanism of acquired resistance to osimertinib in 
patients with T790M is through the BRAF pathway. Simultaneous blockade of the 
BRAF and EGFR had a significant inhibitory effect.