EGFRPolymorphism and Survival of NSCLC Patients Treated with TKIs: A Systematic Review and Meta-Analysis

Abstract

Tyrosine kinase inhibitor- (TKI-) based therapy revolutionized the overall survival and the quality of life in non-small-cell lung cancer (NSCLC) patients that have epidermal growth factor receptor (EGFR) mutations. However, EGFR is a highly polymorphic and mutation-prone gene, with over 1200 single nucleotide polymorphisms (SNPs). Since the role of EFGR polymorphism on the treatment outcome is still a matter of debate, this research analyzed the available literature data, according to the PRISMA guidelines for meta-analyses. Research includes PubMed, Scopus, ISI Web of Science, and 14 of genome-wide association studies (GWAS) electronic databases in order to provide quantitative assessment of the association between ten investigated EGFR SNPs and the survival of NSCLC patients. The pooled HR and their 95% CI for OS and PFS for different EGFR polymorphisms using a random or fixed effect model based on the calculated heterogeneity between the studies was applied. The longest and the shortest median OSs were reported for the homozygous wild genotype and a variant allele carriers for rs712829 (-216G>T), respectively. Quantitative synthesis in our study shows that out of ten investigated EGFR SNPs (rs11543848, rs11568315, rs11977388, rs2075102, rs2227983, rs2293347, rs4947492, rs712829, rs712830, and rs7809028), only four, namely, rs712829 (-216G>T), rs11568315 (CA repeat), rs2293347 (D994D), and rs4947492, have been reported to affect the outcome of TKI-based NSCLC treatment. Of these, only -216G>T and variable CA repeat polymorphisms have been confirmed by meta-analysis of available data to significantly affect OS and PFS in gefitinib- or erlotinib-treated NSCLC patients.

Tumor-targeting anti-EGFR x anti-PD1 bispecific antibody inhibits EGFR-overexpressing tumor growth by combining EGFR blockade and immune activation with direct tumor cell killing

“…EGFR/HER1 is a member of the epidermal growth factor receptor (EGFR) family and plays important roles in development and tumorigenesis, e.g. lung tumors [13 , 14] . HER receptors are often overexpressed or mutated in many tumors and thus are considered as important targets for anti-tumor therapy.…”

A signature of 17 immune-related gene pairs predicts prognosis and immune status in HNSCC patients

“…Heterogeneous subsets of tumor with different molecular targets may lead to different resistance levels to cancer therapy and the progression of final clinical outcomes [5 , 6] . This is mainly due to the presence of heterogeneity of EGFR polymorphisms (variation) and clinical response, and EGFR variations has a better therapy outcome [7 , 8] .…”

Polymorphisms in EGFR Gene Predict Clinical Outcome in Unresectable Non-Small Cell Lung Cancer Treated with Radiotherapy and Platinum-Based Chemoradiotherapy

“…The vast majority of these studies involved small groups of patients. In a very recent meta-analysis, Jurisic et al [ 33 ] summarized the results in NSCLC, showing that rs712829 significantly affected OS and PFS in patients receiving gefitinib or erlotinib. In turn, the largest study among lung cancer patients given RT and standard CHT was carried out in a Chinese population; however, the authors found no relationship between the SNPs we examined and prognosis [ 35 ].…”

“…Research on the predictive and prognostic potential of EGFR SNPs has mainly focused on EGFR-directed therapy with small-molecule tyrosine kinase inhibitors (TKIs) and anti-EGFR monoclonal antibodies (mAbs). Although the results of these studies are not conclusive, some of them show an association between EGFR SNPs and the efficacy of EGFR–targeted treatment in lung cancer as well as in other solid tumors [ 29 , 30 , 31 , 32 , 33 ]. However, very little is known about their possible influence on the effects of RT or CHT with platinum drugs commonly used in NSCLC treatment.…”