Bevacizumab Combined with Icotinib Overcomes Osimertinib Resistance in a Patient of Non-Small-Cell Lung Cancer

A 61-year-old Chinese female patient was diagnosed with primary pulmonary adenocarcinoma of left superior lobe with epidermal growth factor receptor (EGFR) 19 del mutation positive.Treatment with Icotinib was given and her disease progressed after 6 months.CT-guide needle biopsy for the new lesion of inferior lobe of left lung demonstrated metastasis, and EGFR gene panel was test by Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR) confirmed EGFR T790M mutation.Treatment with Osimertinib was initiated.After 2 months remission, the disease progressed.The biopsy was performed for the new tumor of the inferior lobe of the left lung, and ARMS-PCR demonstrated no other gene mutation except EGFR 19 del.Icotinib was re-challenged, but disease progressed quickly.Bevacizumab was added, and after 2-cycle of combination therapy, partial response was achieved.Patients of non-small-cell lung cancer maintain EGFR activating mutation and loss of EGFR T790M mutation is a genetic change after Osimertinib treatment.This case suggests the re-challenge of first-generation EGFR-TKIs combines with bevacizumab may overcome its resistance and prolong patients' survival. EPIDERMAL growth factor receptor (EGFR) C797S/G point mutation or loss of EGFR T790Mwas the most common genetic change in patients with non-small-cell lung cancer (NSCLC) harboring EGFR T790M mutation after resistance to osimertinib. 1,2Anti-EGFR antibody combined with EAI045 or Brigatinib could overcome Osimertinib resistance in vitro or in vivo if it was caused by EGFR L858R/C797S/T790M or EGFR del 19/C797S/T790M. 3,4But their clinical effects are largely unclear.There has been no standard care for patients who lose EGFR T790M mutation after Osimertinib resistance; re-challenge with first generation EGFR tyrosine kinase inhibitor (TKI) or systemic chemotherapy might be the optimal method. 5About 10%-30% Caucasian or 50% eastern Asian patients with NSCLC harbor EGFR mutation, and 60% of them will acquire EGFR T790M mutation after the first generation EGFR-TKI