Effective treatment of pulmonary adenocarcinoma harboring triple EGFR mutations of L858R, T790M, cis-G796s/cis-C797s by osimertinib, brigatinib, and bevacizumab combination therapy: A case report

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) were widely used in advanced non-small cell lung cancers (NSCLCs) with EGFR sensitive mutation and greatly improved the patient survival. With the widespread use of EGFR TKI, TKI resistance is increasingly emerging in the clinic. Osimertinib, a 3rd EGFR-TKI, commonly was used in patients who were resistant to early-generation EGFR-TKIs carrying T790M mutation. After using of osimertinib, it might result in the development of further resistance, for example, the cis-C797S mutation. Herein, we report an effective treatment for a case of advanced pulmonary adenocarcinoma patient with triple EGFR mutations of L858R/T790M/cis-C797S and L858R/T790M/cis-G796S by the combination therapy of osimertinib, brigatinib, and bevacizumab after the combination of brigatinib and cetuximab failed. The plasma circulating tumor DNA (ctDNA) monitoring provided information of EGFR mutation evolution and guided appropriate therapy regimen during the progression. After the combination therapy worked, a significant reduction of the 3 EGFR mutations was detected. The side effect was acceptable during the whole period of therapies.