title: EGFR TKI combination with immunotherapy in non-small cell lung cancer.
abstract: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) has significantly improved clinical outcomes compared with chemotherapy in non-small cell lung cancer (NSCLC) patients with sensitizing EGFR gene mutation. Areas covered: Almost all patients treated with EGFR TKIs eventually develop acquired resistance. It has been reported that activation of the oncogenic EGFR pathway enhances susceptibility of the lung tumors to PD-1 blockade in mouse model, suggesting combination of PD1 blockade with EGFR TKIs may be a promising therapeutic strategy. Nivolumab combined with erlotinib was associated with 19% of grade 3 toxicities. The combination of osimertinib plus durvalumab in pretreated or chemo naïve NSCLC patients showed encouraging clinical activity, however, this combination was associated with high incidence of interstitial lung disease (38%), leading to termination of further enrollment. The combination of gefitinib plus durvalumab demonstrated encouraging activity but higher incidence of grade 3/4 liver enzyme elevation (40-70%). The treatment related Grade 3-4 adverse events were observed in 39% of patients when treated with atezolizumab plus erlotinib. Expert opinion: Given the relatively high incidence of treatment-related toxicities associated with combination of EGFR TKI and immunotherapy, further development of this approach remains controversial. Until now, the combination of EGFR TKI and immunotherapy should be investigational.
authors.affiliation: a Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center , Sungkyunkwan University School of Medicine , Seoul , Korea.
authors.forename: Myung-Ju
authors.initials: MJ
authors.lastname: Ahn
authors.affiliation: a Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center , Sungkyunkwan University School of Medicine , Seoul , Korea.
authors.forename: Jong-Mu
authors.initials: JM
authors.lastname: Sun
authors.affiliation: a Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center , Sungkyunkwan University School of Medicine , Seoul , Korea.
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: a Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center , Sungkyunkwan University School of Medicine , Seoul , Korea.
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Ahn
authors.affiliation: a Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center , Sungkyunkwan University School of Medicine , Seoul , Korea.
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D009154:Mutation; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: EGFR TKI; EGFR mutation; NSCLC; immunotherapy