tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2025-050tumors-1489Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL REPORTSВлияние показателей безопасности и профиля токсичности на эффективность комбинированной терапии первой линии у больных распространенным почечноклеточным раком: исследование реальной клинической практикиImpact of safety parameters and toxicity profile on the efficacy of first-line combination therapy in patients with advanced renal cell carcinoma: a real-world studyhttps://orcid.org/0000-0001-7754-6624ВолковаМ. И.VolkovaM. I.

Волкова Мария Игоревна 

117152 Москва, Загородное шоссе, 18А 

125993 Москва, ул. Баррикадная, 2 / 1, стр. 1 

Volkova Mariya Igorevna

18A Zagorodnoe Shosse, Moscow 117152

1,2/1 Barrikadnaya St.,Moscow 125993

https://orcid.org/0000-0002-7853-0349НерсесоваТ. А.NersesovaT. A.

Татьяна Александровна Нерсесова 

117152 Москва, Загородное шоссе, 18А 

Nersesova Tatyana Aleksandrovna

18A Zagorodnoe Shosse, Moscow 117152

dr.nersesova@gmail.comhttps://orcid.org/0000-0002-9558-5579ЛядоваМ. А.LyadovaM. A.

Лядова Марина Александровна 

117152 Москва, Загородное шоссе, 18А 

125993 Москва, ул. Баррикадная, 2 / 1, стр. 1 

Lyadova Marina Aleksandrovna

18A Zagorodnoe Shosse, Moscow 117152

1,2/1 Barrikadnaya St.,Moscow 125993

https://orcid.org/0009-0007-2856-5176КузьминаЕ. С.KuzminaE. S.

Кузьмина Евгения Сергеевна 

117152 Москва, Загородное шоссе, 18А 

Kuzmina Evgeniya Sergeevna

18A Zagorodnoe Shosse, Moscow 117152

https://orcid.org/0009-0007-6646-7454АнтоноваТ. Г.AntonovaT. G.

Антонова Татьяна Галяутдиновна 

117152 Москва, Загородное шоссе, 18А 

Antonova Tatyana Galyautdinovna

18A Zagorodnoe Shosse, Moscow 117152

https://orcid.org/0009-0006-0637-9826ЦареваЕ. В.TsarevaE. V.

Царева Елена Владимировна 

117152 Москва, Загородное шоссе, 18А 

Tsareva Elena Vladimirovna

18A Zagorodnoe Shosse, Moscow 117152

https://orcid.org/0009-0002-1084-1551СтативкоО. А.StativkoO. A.

Стативко Олеся Алексеевна 

117152 Москва, Загородное шоссе, 18А 

Stativko Olesya Alekseevna

18A Zagorodnoe Shosse, Moscow 117152

https://orcid.org/0000-0003-1258-0922ЧерняевВ. А.ChernyaevV. A.

Черняев Виталий Александрович 

117152 Москва, Загородное шоссе, 18А 

Chernyaev Vitalii Aleksandrovich

18A Zagorodnoe Shosse, Moscow 117152

https://orcid.org/0000-0001-9864-3837ПокатаевИ. А.PokataevI. A.

Покатаев Илья Анатольевич 

117152 Москва, Загородное шоссе, 18А 

Pokataev Ilya Anatolevich

18A Zagorodnoe Shosse, Moscow 117152

Онкологический центр № 1 Городской клинической больницы имени С. С. Юдина Департамента здравоохранения города Москвы ; ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииРоссияOncology Center No. 1 of the City Clinical Hospital named after S. S. Yudin of the Moscow Department of Health ; Russian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaRussian FederationОнкологический центр № 1 Городской клинической больницы имени С. С. Юдина Департамента здравоохранения города МосквыРоссияOncology Center No. 1 of the City Clinical Hospital named after S. S. Yudin of the Moscow Department of HealthRussian Federation202530102025153716Copyright © Волкова М.И., Нерсесова Т.А., Лядова М.А., Кузьмина Е.С., Антонова Т.Г., Царева Е.В., Стативко О.А., Черняев В.А., Покатаев И.А., 20252025Волкова М.И., Нерсесова Т.А., Лядова М.А., Кузьмина Е.С., Антонова Т.Г., Царева Е.В., Стативко О.А., Черняев В.А., Покатаев И.А.Volkova M.I., Nersesova T.A., Lyadova M.A., Kuzmina E.S., Antonova T.G., Tsareva E.V., Stativko O.A., Chernyaev V.A., Pokataev I.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.malignanttumors.org/jour/article/view/1489

Цель: Оценить влияние показателей безопасности и профиля токсичности на эффективность первой линии терапии почечно-клеточного рака (ПКР), основанной на иммуноонкологических препаратах (ИО), в реальной практике.Материал и методы: Критериями включения в ретроспективное исследование являлись возраст ≥ 18 лет, морфологически подтвержденный распространенный ПКР, проведение 1 линии терапии комбинациями, основанными на ИО; критериями исключения — противопоказания к препаратам комбинации, отсутствие данных о ≥ 1 приеме каждого из препаратов комбинации и ≥ 1 контрольном осмотре после старта терапии. Регистрировались все нежелательные явления (НЯ), их характеристики и случаи коррекции лечебного режима из-за НЯ, лучший ответ на лечение, время до прогрессирования, смерти и последнего наблюдения. Проводился анализ потенциальной взаимосвязи показателей безопасности с показателями эффективности терапии 1 линии.Результаты: Включены данные 194 пациентов, получавших ниволумаб с ипилимумабом, ИО-ИО (94 (48,5 %)) или иммуно-таргетную терапию, ИО-ТКИ (100 (51,5 %)). Медиана наблюдения — 28,4 (1–63) месяца. Частота объективного ответа (ЧОО) во всей популяции (ИО-ИО / ТКИ) составила 36,6 %, частота контроля над опухолью (ЧКО) — 79,4 %, медиана беспрогрессивной выживаемости (БПВ) — 20,0 (15,3–24,8) месяцев, общей выживаемости (ОВ) — 29,2 (24,4–34,0) месяца. В группе ИО-ИО / ТКИ независимыми факторами благоприятного прогноза эффективности терапии являлись кожные НЯ (отношение рисков (ОР) для ЧОО 5,9 (95 % доверительный интервал (ДИ): 3,1–38,4), р = 0,002; отношение шансов (ОШ) для БПВ 2,4 (95 % ДИ: 1,2–4,6), р = 0,011), эндокринные НЯ (ОР для ЧОО 2,5 (95 % ДИ: 1,8–3,5), р = 0,021; ОШ для БПВ 2,6 (95 % ДИ: 1,4–4,8), р = 0,002; ОШ для ОВ 2,6 (95 % ДИ: 1,5–4,6), р = 0,001) и гастроинтестинальные (ГИ) НЯ (ОШ для БПВ 1,8 (95 % ДИ: 1,1–3,2), р = 0,030). Независимыми факторами неблагоприятного прогноза ОВ являлись серьезные НЯ (ОШ 24,9 (95 % ДИ: 4,7–130,5), р < 0,0001). Независимым фактором благоприятного прогноза в группе ИО-ИО являлись эндокринные НЯ (ОШ для БПВ 2,1 (95 % ДИ: 1,1–4,1), р = 0,026; ОШ для ОВ 2,8 (95 % ДИ: 1,4–5,6), р = 0,003), в группе ИО-ТКИ — все НЯ (ОШ для ОВ 2,9 (95 % ДИ: 1,1–7,5), р = 0,033), кожные НЯ (ОР для ЧОО — 3,1 (95 % ДИ: 1,2–6,2), р = 0,04; ОШ для БПВ 3,0 (95 % ДИ: 1,2–7,6), р = 0,021), ГИ НЯ (ОШ для БПВ 3,3 (95 % ДИ: 1,5–7,2), р = 0,002) и эндокринные НЯ (ОШ для БПВ 3,3 (95 % ДИ: 1,6–6,7), р = 0,001).Выводы: Развитие НЯ у пациентов с ПКР ассоциировано с улучшением показателей эффективности ИО-основанной комбинированной терапии. Возможность использования НЯ в качестве потенциального маркера клинической пользы ИО-основанной комбинированной терапии требует подтверждения в проспективных исследованиях.

Objective

Objective: To evaluate the impact of safety parameters and toxicity profile on the efficacy of first-line immuno-oncology (IO) — based therapy in patients with renal cell carcinoma (RCC) in real-world clinical practice. 

Materials and Methods

Materials and Methods: Inclusion criteria for this retrospective study were: age ≥ 18 years, histologically confirmed advanced RCC, and administration of first-line therapy with IO-based combination regimens. Exclusion criteria included contraindications to any combination therapy agents, lack of data on at least one administration of each combination agent, and absence of at least one follow-up examination after treatment initiation. All adverse events (AEs), their characteristics, and instances of treatment regimen modification due to AEs were documented, along with the best overall response to therapy, time to progression, time to death, and last follow-up. An analysis of the potential association between safety parameters and first-line therapy efficacy outcomes was performed. 

Results

Results: Data from 194 patients were included, receiving either nivolumab with ipilimumab (IO — IO), 94 patients (48.5 %) or immuno-targeted therapy (IO — TKI) 100 patients (51.5 %). Median follow-up duration was 28.4 months (1–63 months). The objective response rate (ORR) in the entire population (IO — IO / TKI) was 36.6 %, disease control rate (DCR) was 79.4 %, median progression-free survival (PFS) was 20.0 months (95 % CI, 15.3–24.8), and median overall survival (OS) was 29.2 months (95 % CI, 24.4–34.0). In the IO — IO / TKI group, independent favorable prognostic factors for therapy efficacy were cutaneous AEs (risk ratio [RR] for ORR 5.9 [95 % confidence interval (CI): 3.1–38.4], p = 0.002; odds ratio [OR] for PFS 2.4 [95 % CI: 1.2–4.6], p = 0.011), endocrine AEs (RR for ORR 2.5 [95 % CI: 1.8–3.5], p = 0.021; OR for PFS 2.6 [95 % CI: 1.4–4.8], p = 0.002; OR for overall survival [OS] 2.6 [95 % CI: 1.5–4.6], p = 0.001), and gastrointestinal (GI) AEs (OR for PFS 1.8 [95 % CI: 1.1–3.2], p = 0.030). Independent unfavorable prognostic factors for OS were serious AEs (OR 24.9 [95 % CI: 4.7–130.5], p < 0.0001).Independent favorable prognostic factors in the IO — IO group were endocrine AEs (OR for PFS 2.1 [95 % CI: 1.1–4.1], p = 0.026; OR for OS 2.8 [95 % CI: 1.4–5.6], p = 0.003), while in the IO — TKI group, favorable prognostic factors included the occurrence of any AEs (OR for OS 2.9 [95 % CI: 1.1–7.5], p = 0.033), cutaneous AEs (RR for ORR 3.1 [95 % CI: 1.2–6.2], p = 0.04; OR for PFS 3.0 [95 % CI: 1.2–7.6], p = 0.021), GI AEs (OR for PFS 3.3 [95 % CI: 1.5–7.2], p = 0.002), and endocrine AEs (OR for PFS 3.3 [95 % CI: 1.6–6.7], p = 0.001).

Conclusions

Conclusions: The development of AEs in patients with RCC is associated with improved efficacy outcomes of IO based combination therapy. The potential use of AEs as biomarkers of clinical benefit from IO-based combination therapy warrants confirmation in prospective studies.

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