Journal of Modern OncologyJournal of Modern OncologyСовременная онкология1815-14341815-1442LLC Obyedinennaya Redaktsiya8118610.26442/18151434.2021.3.201111CLINICAL ONCOLOGYКЛИНИЧЕСКАЯ ОНКОЛОГИЯResearch ArticleComparison of afatinib and osimertinib effect on overall survival in first-line drug treatment of EGFR-positive metastatic non-small cell lung cancer: network meta-analysisСравнение влияния афатиниба и осимертиниба на общую выживаемость в 1-й линии лекарственного лечения EGFR-положительного метастатического немелкоклеточного рака легкого: сетевой метаанализhttps://orcid.org/0000-0002-6884-3499GoryaynovSergey V.ГоряйновСергей Вадимович
Russian Federation

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Background. Tyrosine kinase inhibitors (TKIs) are the standard of treatment of EGFR-positive metastatic non-small cell lung cancer (mNSCLC). Different TKI generations have different properties. Currently there are no results of head-to-head clinical trials of II generation TKI afatinib against III generation TKI osimertinib. In such case network meta-analysis (NMA) can be used for evidence synthesis.

Aim. To compare afatinib and osimertinib effect on overall survival (OS) in first-line drug treatment of EGFR-positive mNSCLC.

Materials and methods. Search of trials to build evidence network was done in Medline, CT.gov, and EU-CTR. Endpoint was OS measured as hazard ratio (HR) of all-cause death. Analysis was split into base case analysis and two sensitivity analyses depending on criteria of transitivity. Random effect model was used for NMA. Results were analyzed in overall population and subgroups according to the type of EGFR-mutation, ECOG score, and presence of CNS metastases. Statistical analysis was done in R with netmeta package.

Results. Fourteen trials were included in the study. There was no statistically significant difference regarding OS between afatinib and osimertinib in overall population neither in base case nor in first sensitivity analysis: HR 1.06 [0.79; 1.41], p=0.697 and 1.08 [0.83; 1.41], p=0.561, respectively. Results of comparison of II generation TKIs against osimertinib in second sensitivity analysis were consistent: HR 1.03 [0.81; 1.31], p=0.834. Results in all subgroups were consistent with each other and overall population. There was no statistically significant heterogeneity/inconsistency in the network in any of the analyses.

Conclusion. Afatinib and osimertinib have similar efficacy regarding OS in first-line drug treatment of EGFR-positive mNSCLC.

Обоснование. Ингибиторы тирозинкиназы (ИТК) являются стандартом лечения EGFR-положительного метастатического немелкоклеточного рака легкого (мНМРЛ). Разные поколения ИТК отличаются по своим свойствам. Сейчас отсутствуют результаты прямых сравнительных клинических испытаний ИТК II поколения афатиниба и ИТК III поколения осимертиниба. В этой ситуации получить необходимые доказательства можно при помощи сетевого метаанализа.

Цель. Сравнить афатиниб и осимертиниб по влиянию на общую выживаемость (ОВ) в 1-й линии лекарственного лечения EGFR-положительного мНМРЛ.

Материалы и методы. Поиск исследований для построения сети доказательств проводился в базах Medline, CT.gov и EU-CTR. Конечной точкой являлась ОВ, представленная в виде относительного риска (ОР) смерти от всех причин. Исследование состояло из базового анализа и двух анализов чувствительности, выделенных на основании строгости критериев соблюдения допущения транзитивности. Сетевой метаанализ выполнен с использованием модели случайного эффекта. Результаты рассчитывались в общей популяции и подгруппах согласно типу EGFR-мутации, наличию метастазов в центральной нервной системе и баллу по шкале ECOG. Статистический анализ проводился в приложении R с использованием пакета netmeta.

Результаты. Всего для анализа отобрано 14 исследований. В общей популяции не имелось статистически значимой разницы между афатинибом и осимертинибом по влиянию на ОВ ни в основном анализе, ни в 1-м анализе чувствительности: ОР 1,06 [0,79; 1,41], p=0,697 и 1,08 [0,83; 1,41], p=0,561 соответственно. С ними согласовывались результаты сравнения ИТК II поколения в целом с осимертинибом во 2-м анализе чувствительности: ОР 1,03 [0,81; 1,31], p=0,834. Результаты анализа во всех подгруппах полностью согласовывались друг с другом и с анализом в общей популяции. Ни в одном из анализов в сети не было статистически значимой гетерогенности/рассогласованности.

Заключение. Афатиниб и осимертиниб обладают схожей эффективностью по влиянию на ОВ в 1-й линии лекарственного лечения EGFR-положительного мНМРЛ.

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