Comparison of the efficacy of first-line therapy with different generations of EGFR tyrosine kinase inhibitors in patients with advanced EGFR-associated non-small cell lung cancer: a network meta-analysis of overall survival data

Abstract

The lack of trials directly comparing 2nd and 3rd generation EGFR tyrosine kinase inhibitors (TKI) do not allows to determine the optimal treatment approach. The main objective of this study was to compare the survival advantage achieved with these options. Materials and methods. As a result of a systematic search in the PubMed, ClinicalTrials.gov databases, as well as in the materials of international conferences American Society of Clinical Oncology and European Society for Medical Oncology data on the overall survival showed in 11 open randomized trials comparing different generation TKI monotherapy in TKI nave EGFR mutated non-small-cell lung carcinoma (NSCLC), both in the general population and in subgroups including sex, age, mutational status, smoking status. Using the package netmeta for the programming language R, a network meta-analysis of the obtained data was carried out using a frequency framework. Results. The 11 selected studies, including 3251 participants, had the following comparison groups: 6 studies (ENSURE, EURTAC, IPASS, NEJ002, OPTIMAL CTONG-0802, WJTOG3405) compared 1st generation TKIs and standard platinum-based drugs (CT); 2 studies (LUX-Lung 3, LUX-Lung 6) compared 2nd generation TKIs and CT; 2 studies (ARCHER 1050, LUX-Lung 7) compared 2nd generation TKIs and 1st generation TKIs; one study (FLAURA) compared 3rd generation TKI and the 1st generation TKIs. It was shown that for overall survival in comparison with CT, 3rd generation TKIs [hazard ratio HR 0.84 (0.64; 1.08) and 2nd generation (HR 0.86 (0.74; 1.00)] have the same effectiveness. Subgroup analysis did not reveal significant differences in OS except for the subgroup of patients with a deletion in exon 19 of the EGFR gene, where the use of 2nd generation TKIs in comparison with CT had a statistically significant difference HR 0.71 (0.37; 0.97). Conclusions. The network meta-analysis of the overall survival data of clinical trials of the use of different generations TKIs as the first line treatment in patients with EGFR-associated NSCLC showed that the use of TKIs of the 3rd and 2nd generation has the same efficacy, and the TKIs of the 2nd generation increase the total survival in a group of patients carrying a mutation in exon 19 of the EGFR gene.

Keywords

• non-small-cell lung carcinoma
• egfr
• tyrosine kinase inhibitors
• overall survival