medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2024-243medsovet-8391Research ArticleИММУНОТЕРАПИЯIMMUNOTHERAPYПредикторы эффективности иммунохимиотерапии атезолизумабом в комбинации с этопозидом и карбоплатином у больных распространенным мелкоклеточным раком легкогоPredictors of the immunochemotherapy effectiveness of atezolizumab in combination with etoposide and carboplatin in patients with advanced small cell lung cancerhttps://orcid.org/0000-0002-1357-0956КузьминовА. Е.KuzminovA. E.

Кузьминов Александр Евгеньевич - к.м.н., научный сотрудник отделения противоопухолевой лекарственной терапии №3 отдела лекарственного лечения.

115478, Москва, Каширское шоссе, д. 23

Alexander E. Kuzminov - Cand. Sci. (Med.), Researcher of Cancer Drug Therapy Department No. 3.

23, Kashirskoye Shosse, Moscow, 115478

alexkouzminov@mail.ruhttps://orcid.org/0000-0002-4548-1026БарболинаТ. Д.BarbolinaT. D.

Барболина Татьяна Дмитриевна - к.м.н., врач-онколог отделения противоопухолевой лекарственной терапии №3 отдела лекарственного лечения, НМИЦО имени Н.Н. Блохина; ассистент кафедры онкологии факультета постдипломного дополнительного образования, РосУниМед.

115478, Москва, Каширское шоссе, д. 23;127473, Москва, ул. Делегатская, д. 20, стр. 1

Tatyana D. Barbolina - Candidate of Medical Sciences, Oncologist of Cancer Drug Therapy Department No. 3, Blokhin NMRCO; Assistant of the Oncology Department, Faculty of Postgraduate Additional Education, ROSUNIMED.

23, Kashirskoye Shosse, Moscow, 115478; 20, Bldg. 1, Delegatskaya St., Moscow, 127473

katan4ik@list.ruhttps://orcid.org/0000-0002-2154-3376РеутоваЕ. В.ReutovaE. V.

Реутова Елена Валерьевна - к.м.н., старший научный сотрудник отделения противоопухолевой лекарственной терапии №3 отдела лекарственного лечения.

115478, Москва, Каширское шоссе, д. 23

Elena V. Reutova - Cand. Sci. (Med.), Senior Researcher of Cancer Drug Therapy Department No. 3.

23, Kashirskoye Shosse, Moscow, 115478

ereutova@rambler.ruhttps://orcid.org/0000-0002-0620-2696ЮдинД. И.YudinD. I.

Юдин Денис Иванович - к.м.н., старший научный сотрудник отделения противоопухолевой лекарственной терапии №3 отдела лекарственного лечения.

115478, Москва, Каширское шоссе, д. 23

Denis I. Yudin - Cand. Sci. (Med.), Senior Researcher of Cancer Drug Therapy Department No. 3.

23, Kashirskoye Shosse, Moscow, 115478

yudinden@mail.ruhttps://orcid.org/0000-0002-6244-4294БредерВ. В.BrederV. V.

Бредер Валерий Владимирович - д.м.н., заведующий лекарственным отделом.

115478, Москва, Каширское шоссе, д. 23

Valeriy V. Breder - Dr. Sci. (Med.), Head of the Medicine Department.

23, Kashirskoye Shosse, Moscow, 115478, Russia; AuthorID: 280121

vbreder@yandex.ruhttps://orcid.org/0000-0003-4469-502XЛактионовК. К.LaktionovK. K.

Лактионов Константин Константинович - д.м.н., заместитель директора, заведующий отделением противоопухолевой лекарственной терапии №3 отдела лекарственного лечения, НМИЦО имени Н.Н. Блохина; профессор, профессор кафедры онкологии и лучевой терапии лечебного факультета, РНИМУ имени Н.И. Пирогова.

115478, Москва, Каширское шоссе, д. 23; 117997, Москва, ул. Островитянова, д. 1

Konstantin K. Laktionov - Dr. Sci. (Med.), Deputy Director, Head of Department of Cancer Drug Therapy Department No. 3, Blokhin NMRCO; Professor of the Department of Oncology and Radiation Therapy, Faculty of Medicine, Pirogov RNRMU.

23, Kashirskoye Shosse, Moscow, 115478; 1, Ostrovityanov St., Moscow, 117997

lkoskos@mail.ruНациональный медицинский исследовательский центр онкологии имени Н.Н. БлохинаРоссияBlokhin National Medical Research Center of OncologyRussian FederationНациональный медицинский исследовательский центр онкологии имени Н.Н. Блохина; Российский университет медицины (РосУниМед)РоссияBlokhin National Medical Research Center of Oncology; Russian University of Medicine (ROSUNIMED)Russian FederationНациональный медицинский исследовательский центр онкологии имени Н.Н. Блохина; Российский национальный исследовательский медицинский университет имени Н.И. ПироговаРоссияBlokhin National Medical Research Center of Oncology; Pirogov Russian National Research Medical UniversityRussian Federation2024240720240102835Copyright © Кузьминов А.Е., Барболина Т.Д., Реутова Е.В., Юдин Д.И., Бредер В.В., Лактионов К.К., 20242024Кузьминов А.Е., Барболина Т.Д., Реутова Е.В., Юдин Д.И., Бредер В.В., Лактионов К.К.Kuzminov A.E., Barbolina T.D., Reutova E.V., Yudin D.I., Breder V.V., Laktionov K.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/8391Введение

Введение. Рак легкого остается ведущей причиной смерти среди онкологических заболеваний в мире. Впервые за последние 30 лет в рандомизированных клинических исследованиях с применением иммунохимиотерапии отмечено достоверное увеличение медианы общей выживаемости у пациентов с распространенным мелкоклеточным раком легкого. Однако не было выявлено значимых предикторов эффективности иммунохимиотерапии.

Цель

Цель. Улучшить отдаленные результаты лечения пациентов с распространенным мелкоклеточным раком легкого с помощью поиска предикторов эффективности иммунохимиотерапии.

Материалы и методы

Материалы и методы. Всего в анализ включены 35 пациентов с распространенным мелкоклеточным раком легкого, получивших в качестве 1-й линии лечения иммунохимиотерапию атезолизумабом в комбинации с этопозидом и карбоплатином, – 11 женщин и 24 мужчины. Средний возраст составил 61 год. На момент начала иммунохимиотерапии была стадия IVA у 10 пациентов, IVB – у 24 и IIIБ – у 1. Проведена ретроспективная оценка прогностического влияния на медиану выживаемости без прогрессирования и общей выживаемости таких факторов, как лейкоцитоз, тромбоцитоз, уровень лактатдегидрогеназы, соотношение нейтрофилов и лимфоцитов, уровень фибриногена, группа крови.

Результаты

Результаты. Медиана выживаемости без прогрессирования составила 6,2 (95% ДИ 4,6–7,8) мес., медиана общей выживаемости – 16,0 (95% ДИ 9,4–22,6) мес. Отмечена тенденция к увеличению медианы выживаемости без прогрессирования, но без статистически значимых различий при лейкоцитозе, тромбоцитозе, повышенном уровне фибриногена и нормальном уровне лактатдегидрогеназы на момент начала лечения. Значимое влияние на медиану выживаемости без прогрессирования оказало соотношение количества нейтрофилов и лимфоцитов на момент начала лечения. При уровне соотношения количества нейтрофилов и лимфоцитов менее 3 происходило статистически достоверное увеличение медианы выживаемости без прогрессирования с 4,5 (95% ДИ 3,9–5,1) до 6,9 (95% ДИ 5,6–8,2) мес. Также получено достоверное уменьшение медианы выживаемости без прогрессирования у пациентов с группой крови B (III) – 5,0 (95% ДИ 3,5–6,5) против 6,2 (95% ДИ 4,7–7,7) мес. у пациентов с другой группой крови (р = 0,047). Достоверного влияния на общую выживаемость не оказывали такие факторы, как лейкоцитоз, тромбоцитоз, уровень фибриногена, уровень лактатдегидрогеназы и соотношение количества нейтрофилов и лимфоцитов. Группа крови B (III) значимо ухудшала продолжительность жизни пациентов: медиана общей выживаемости составила 12,1 (95% ДИ 9,3–14,9) мес. при группе крови B (III) и не была достигнута у пациентов с другой группой крови (р = 0,017).

Заключение

Заключение. Достоверность выявленных предикторов эффективности иммунохимиотерапии у больных распространенным мелкоклеточным раком легкого должна быть подтверждена на большей выборке с применением многофакторного анализа. Продолжается набор пациентов в исследование.

Introduction

Introduction. Lung cancer remains the leading cause of cancer-related deaths worldwide. For the first time in 30 years, the randomized clinical studies employing immunochemotherapy showed a significant increase in median overall survival for patients with advanced small cell lung cancer. However, no significant predictors of the immunochemotherapy effectiveness were identified.

Aim

Aim. To improve long-term outcomes of treatment of patients with advanced small cell lung cancer through search for predictors of the immunochemotherapy effectiveness.

Materials and methods

Materials and methods. A total of 35 patients (11 women and 24 men) with advanced small cell lung cancer who received immunochemotherapy with atezolizumab combined with etoposide and carboplatin as first-line treatment were included in the analysis. The average age for patients was 61 years. At the immunochemotherapy baseline, 10 patients had stage IVA disease, 24 patients had stage IVB disease, and one patient had stage IIIB disease. We retrospectively assessed the prognostic impact on the median progression-free survival and overall survival of such factors as leukocytosis, thrombocytosis, lactate dehydrogenase level, neutrophil to lymphocyte ratio, fibrinogen level, blood type.

Results

Results. Median progression-free survival was 6.2 (95% CI 4.6–7.8) months, median overall survival was 16.0 (95% CI 9.4– 22.6) months. There was an increasing trend in median progression-free survival, but without statistically significant differences in leukocytosis, thrombocytosis, elevated fibrinogen levels and normal lactate dehydrogenase levels at the beginning of therapy. The neutrophil to lymphocyte ratio at the beginning of therapy had a significant impact on median progression-free survival. There was a statistically significant increase in median progression-free survival from 4.5 (95% CI 3.9–5.1) to 6.9 (95% CI 5.6–8.2) months when the neutrophil to lymphocyte ratio was < 3. A significant decrease in median progression-free survival – 5.0 (95% CI 3.5–6.5) months was also observed in patients with blood group B (III) vs 6.2 (95% CI 4.7–7.7) months for patients with a different blood group (p = 0.047). Factors such as leukocytosis, thrombocytosis, fibrinogen level, lactate dehydrogenase level and neutrophil to lymphocyte ratio did not have a significant impact on overall survival. Patients with blood type B (III) showed significantly worse survival: median overall survival was 12.1 (95% CI 9.3–14.9) months in blood group B (III) and was not achieved in patients with other blood groups (p = 0.017).

Conclusion

Conclusion. The significance of the identified predictors of the immunochemotherapy effectiveness in patients with advanced small cell lung cancer should be confirmed with the larger sampling size using a multivariate analysis. The study continues a recruitment of patients.

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The authors declare that there are no conflicts of interest present.