Patients with Exon 19 Deletion Were Associated with Longer Progression-Free Survival Compared to Those with L858R Mutation after First-Line EGFR-TKIs for Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

Abstract

BackgroundsIt has been extensively proved that the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is superior to that of cytotoxic chemotherapy in advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, the question of whether the efficacy of EGFR-TKIs differs between exon 19 deletion and exon 21 L858R mutation has not been yet statistically answered.MethodsSubgroup data on hazard ratio (HR) for progression-free survival (PFS) of correlative studies were extracted and synthesized based on random-effect model. Comparison of outcomes between specific mutations was estimated through indirect and direct methods, respectively.ResultsA total of 13 studies of advanced NSCLC patients with either 19 or 21 exon alteration receiving first-line EGFR-TKIs were included. Based on the data from six clinical trials for indirect meta-analysis, the pooled HRTKI/chemotherapy for PFS were 0.28 (95% CI 0.20–0.38, P<0.001) in patients with 19 exon deletion and 0.47 (95% CI 0.35–0.64, P<0.001) in those with exon 21 L858R mutation. Indirect comparison revealed that the patients with exon 19 deletion had longer PFS than those with exon 21 L858R mutation (HR19 exon deletion/exon 21 L858R mutation = 0.59, 95% CI 0.38–0.92; P = 0.019). Additionally, direct meta-analysis showed similar result (HR19 exon deletion/exon 21 L858R mutation = 0.75, 95% CI 0.65 to 0.85; P<0.001) by incorporating another seven studies.ConclusionsFor advanced NSCLC patients, exon 19 deletion might be associated with longer PFS compared to L858 mutation at exon 21 after first-line EGFR-TKIs.

Icotinib combined whole brain radiotherapy for patients with brain metastasis from lung adenocarcinoma harboring epidermal growth factor receptor mutation

“…However, only 42 patients (39.6%) in this study received the EGFR-TKI treatment. Although the roles of the exon 19 deletion and exon 21 L858R mutation in EGFR mutation remain controversial, our results, which are in line with those of previous studies (29,30), show that NSCLC with exon 19 deletions or NSCLC with exon 21 L858R are two types of malignancies with different clinical characteristics and pathogenesis. The exact mechanisms for achieving satisfactory outcomes in exon 19 deletion remain unclear.…”

“…The median CPFS time of those patients with exon 19 deletion was substantially increased to 12.0 months. In a meta-analysis (29), those patients with exon 19 deletion showed a longer PFS than those with exon 21 L858R mutations (HR =0.75, 95% CI, 0.65 to 0.85; P<0.001). Li et al (30) reviewed 106 NSCLC patients with brain metastasis from NSCLC.…”

Comparison of Chemotherapy Response and Adverse Effects of Double-Platinum Plus Egfr-Tki Versus Double-Platinum Alone on NSLCLC Patients With Disease Progression and Egfr-Tki Treatment

“…Exon 19 has stronger bonds with TKI (gefitinib) than exon 21, leading to more dominant exon 21 pro-gressive diseases. The meta-analysis study by Zhang et al (2014) from 13 studies found that exon 19 had progression free survival longer than exon 21 in the administration of gefitinib as first line. Three hypo-theses had been developed today that exon 19 has greater affinity for EGF receptors than exon 21.…”

“…Three hypo-theses had been developed today that exon 19 has greater affinity for EGF receptors than exon 21. T790M, as a secondary mutation that is resistant to TKI, more commonly occurs with exon 21 L858R, which is a point mutation with the largest proportion of exon 21 and exon 18 (G719S) which more often appear along with exon 21 (L858R) (Zhang et al 2014).…”

“…The most common cause of TKI EGFR resistance is mutation in EGFR gene which is ex-20-T790M mutation. However, there are many other causes other than the 20-T790M exon mutation, which is MET or PI3K mutation, that may transform into small cell lung cancer (Lin et al 2014, Zhang et al 2014 Side effects were assessed after chemotherapy each cycle. Therapeutic side effects generally appeared in the first cycle.…”