<p>First-line tyrosine kinase inhibitors in EGFR mutation-positive non-small-cell lung cancer: a network meta-analysis</p>

Abstract

Background EGFR-tyrosine kinase inhibitors (EGFR-TKIs) including afatinib, dacomitinib, erlotinib, gefitinib, and osimertinib have proven efficacy in terms of progression-free survival (PFS) in patients with non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, an overall view for comparing efficacy and toxicity on a meta-level is lacking. This study compared efficacy and toxicity of first-line treatment with five different EGFR-TKIs by conducting a network meta-analysis (NMA). Methods A systematic review was performed, aiming to find eligible literature. Data of PFS, overall survival (OS), objective response rate (ORR), and adverse events were extracted. An NMA based on Bayesian statistics was established to synthesize the efficacy and toxicity of all treatments. Results Thirteen randomized controlled trials, including data from 3,539 patients with EGFR-mutated NSCLC, were analyzed. Rank probabilities showed that osimertinib had a potentially better efficacy in terms of PFS and OS compared to all other TKIs. For ORR, afatinib and osimertinib showed a trend of superiority compared to the other four TKIs. Furthermore, there was a high risk of diarrhea and rash for patients treated with afatinib or dacomitinib as well as a moderate risk for treatment with erlotinib, gefitinib, and osimertinib. Conclusion Our study showed a favorable efficacy of osimertinib in terms of PFS and OS compared to all other EGFR-TKIs in patients with NSCLC harboring activating EGFR mutations. Furthermore, gefitinib, erlotinib, and osimertinib were associated with fewer toxicities compared to the other TKIs. Therefore, osimertinib is indicated as a preferable first-line TKI in patients with activating EGFR-mutated NSCLC.

Real-world use of osimertinib for epidermal growth factor receptor T790M-positive non-small cell lung cancer in Japan

“…Although the introduction of EGFR-TKIs into the treatment paradigm for NSCLC improved clinical outcomes for patients ( 4 , 19 ), these agents are associated with several kinds of ADRs, particularly diarrhoea and rash ( 20–22 ). However, a recent network meta-analysis suggested that osimertinib provided an improved benefit-risk profile compared with other EGFR-TKIs ( 23 ).…”

Tumor-Derived Exosomes in Immunosuppression and Immunotherapy

“…Exosomal DNA analysis allows the detection of tumor-specific mutations, which, in the case of heterogeneous solid tumors, can give a more accurate picture of tumor genetics overall than small tissue biopsies [46]. The presence of the mutated epidermal growth factor receptor (EGFR) alleles in exoDNA, especially mutations such as exon 19 Del and exon 21 L858R, characteristic of lung cancer cells, may be important when selecting patients for targeted therapy using a tyrosine kinase inhibitor [40,47]. It has also been shown that mtDNA present in fibroblastderived exosomes activates oxidative phosphorylation (OXPHOS) in breast cancer cells, which leads to resistance to hormone therapy in OXPHOS-dependent breast cancer [48].…”

Cost-effectiveness analysis of the first-line EGFR-TKIs in patients with non-small cell lung cancer harbouring EGFR mutations

“…Therefore, a fixed-effect NMA was considered as appropriate. The methods of the NMA are described in more detail in Appendix I and in a previous study [34]. The results of the NMA are presented in Table 1.…”