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

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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 naïve 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.

作者简介

Alexey Bogdanov

Saint Petersburg Clinical Research and Practice Centre for Specialized Types of Medical Care (Oncological)

编辑信件的主要联系方式.
Email: aleks_aa@mail.ru
ORCID iD: 0000-0002-7887-4635

Cand. Sci. (Phys.-Math.)

俄罗斯联邦, Saint Petersburg

Fedor Moiseenko

Saint Petersburg Clinical Research and Practice Centre for Specialized Types of Medical Care (Oncological)

Email: moiseenkofv@gmail.com
ORCID iD: 0000-0003-2544-9042

D. Sci. (Med.)

俄罗斯联邦, Saint Petersburg

Vitalii Egorenkov

Saint Petersburg Clinical Research and Practice Centre for Specialized Types of Medical Care (Oncological)

Email: v.egorenkov@inbox.ru

Cand. Sci. (Med.)

俄罗斯联邦, Saint Petersburg

Andrey Bogdanov

Saint Petersburg Clinical Research and Practice Centre for Specialized Types of Medical Care (Oncological)

Email: vip.nasa@bk.ru

Research Assistant

俄罗斯联邦, Saint Petersburg

Nikita Volkov

Saint Petersburg Clinical Research and Practice Centre for Specialized Types of Medical Care (Oncological)

Email: volkovnm@gmail.com

Cand. Sci. (Med.)

俄罗斯联邦, Saint Petersburg

Mikhail Fedyanin

Blokhin National Medical Research Center of Oncology; People’s Friendship University of Russia

Email: fedianinmu@mail.ru
ORCID iD: 0000-0001-5615-7806

D. Sci. (Med.)

俄罗斯联邦, Moscow; Moscow

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2. Fig. 1. Study selection scheme for inclusion in network meta-analysis.

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3. Fig. 2. Network plot of comparisons.

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4. Fig. 4. Forest plot obtained in network meta-analysis comparing the efficiency of TKI used in first line therapy of patients harboring exon 19 EGFR mutation versus CT in terms of OS.

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