To be, or not to be: the dilemma of immunotherapy for non-small cell lung cancer harboring various driver mutations

Abstract

IntroductionLung cancer is one of primary cancer type with high incidence and mortality, non-small cell lung cancer (NSCLC) is the most common type of lung cncer. For advanced lung cancer, traditional chemotherapy and targeted therapy become difficult to solve the dilemma of further progress. In recent years, with the clinical application of immunotherapy, the therapeutic strategy of lung cancer has changed dramatically. At present, immunotherapy has shown conspicuous efficacy in NSCLC patients with high expression of programmed death-ligand 1 (PD-L1) and high tumor mutational burden (TMB). The discovery of driver mutations brings delightful hope for targeted cancer therapy. However, it remains controversial whether immunotherapy can be used in NSCLC patients with these specific driver mutations.MethodThis article summarized the latest research progresses of immunotherapy in advanced NSCLC. We paid close attention to the relevance of various driver mutations and immunotherapy in NSCLC patients, and summarized the predictive effects of several driver mutations and immunotherapy.ResultsThe mutations of KRAS, KRAS+TP53, EPHA (especially EPHA5), ZFHX3, ZFHX3+TP53, NOTCH, BRAF and LRP1B+FAT3 have potential to be used as biomarkers to predict the positive effectiveness of immunotherapy. ZFHX3, ZFHX3+TP53, STKII/LKB1+KEAP1+SMARCA4+PBRM1 mutations in LUAD patients get more positive effect in immunotherapy. While the mutations of EGFR, KEAP1, STKII/LKB1+KRAS, EML4-ALK, MET exon 14 skipping mutation, PBRM1, STKII/LKB1+KEAP1+SMARCA4+PBRM1, ERBB2, PIK3CA and RET often indicate poor benefit from immunotherapy.ConclusionMany gene mutations have been shown to be associated with immunotherapy efficacy. Gene mutations should be combined with PD-L1, TMB, etc. to predict the effect of immunotherapy.