Результаты применения рамуцирумаба с иринотеканом и фторпиримидинами во второй линии лечения больных диссеминированным раком желудка

Журнал "Медицинский совет. Онкология" №10, 2019

DOI: https://doi.org/10.21518/2079-701X-2019-10-100-109

Н.С. Бесова¹, Т.А. Титова¹, Д.Л. Строяковский², Е.В. Перминова², С.Г. Багрова¹, Е.С. Обаревич¹, В.А. Горбунова¹, Е.В. Артамонова¹, И.С. Стилиди¹, ¹ Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Министерства здравоохранения Российской Федерации, ² Государственное бюджетное учреждение здравоохранения города Москвы «Московская городская онкологическая больница №62 Департамента здравоохранения города Москвы»

Введение: рамуцирумаб в монотерапии или в комбинации с паклитакселом является стандартом лекарственной терапии 2-й линии при диссеминированном раке желудка (дРЖ). В клинических исследованиях II фазы показана высокая эффективность режимов химиотерапии на основе иринотекана и фторпиримидинов во второй линии лечения больных дРЖ. Целью нашего исследования является оценка эффективности комбинации рамуцирумаба с FOLFIRI/XELIRI в качестве терапии 2-й линии при дРЖ.

Методы: в исследование были включены пациенты с дРЖ с зарегистрированным прогрессированием болезни во время терапии 1-й линии или в течение 4 месяцев после ее завершения. Больные получали рамуцирумаб в комбинации с FOLFIRI (8 мг/кг в 1-й день каждого цикла) или в комбинации с XELIRI (8 мг/кг в 1-й, 8-й дни каждого цикла). Первичной конечной точкой исследования была выживаемость без прогрессирования (ВБП), вторичными точками – частота достижения контроля болезни (КБ) и переносимость.

Результаты: с сентября 2015 г. по апрель 2019 г. в исследование включено 39 пациентов, оценено 38. Медиана количества циклов, проведенных одному больному, – 9 (от 2 до 22). При медиане наблюдения 7,5 месяца медиана ВБП (МВБП) составила 7,6 месяца (95% ДИ: 6,6–8,5), медиана общей выживаемости (МОВ) не достигнута. Объективный эффект (ОЭ) составил 17,9%, стабилизация болезни – 74,4%, таким образом, контроль болезни достигнут у 92,3% больных. Токсичность 3–4-й степени была представлена анемией (2,6%), нейтропенией (18,4%) и диареей (4,3%). Наиболее частыми видами специфической токсичности любой степени были гипертензия (42,1%), кровотечение (26,3%), протеинурия (15,7%) и тромбозы (26,3%). Перфорация полого органа была зафиксирована у 2 пациентов (5,3%). Летальных исходов, связанных с лечением, не зарегистрировано.

Заключение: рамуцирумаб в комбинации с иринотеканом и фторпиримидинами демонстрирует высокую активность и управляемый профиль токсичности во 2-й линии лекарственной терапии пациентов с дРЖ.

Results of the use of ramucirumab in combination with irinotecan and fluoropyrimidines in the second-line chemotherapy for disseminated gastric cancer

Natalia S. Besova¹, Tatiana A. Titova¹, Daniil L. Stroyakovsky², Evgenia V. Perminova², Svetlana G. Bagrova¹, Ekaterina S. Obarevich¹, Vera A. Gorbunova¹, Elena V. Artamonova¹, I.S. Stilidi¹, ¹ Federal State Budgetary Institution «Blokhin Russian Cancer Research Center» of the Ministry of Health of the Russian Federation, ² State Budgetary Healthcare Institution of Moscow «Moscow City Cancer Hospital No 62 of the Moscow Department of Health»

Background: Several studies show that the combination chemotherapy with ramucirumab allows to improve the treatment results of advanced gastric cancer (GC). Irinotecan with fluoropyrimidines is own of the second line chemotherapy options for these patients. As angiogenesis inhibitors can enhance the efficacy of chemotherapy, we investigated the combination of irinotecan and fluoropyrimidines with ramucirumab in metastatic GC. Methods: Eligible patients had advanced morphologically verified GC and disease progression during or within 4 months following first-line therapy. They received FOLFIRI plus ramucirumab (8 mg/kg on day 1) or XELIRI in combination with ramucirumab (8 mg/kg on days 1 and 8). The primary end point was progression-free survival (PFS). Secondary end-points were disease control rate (DCR) and safety. Results: Between September 2015 and April 2019, 39 patients (pts) were enrolled and 38 were evaluated for efficacy and toxicity. Median number of cycles was 9 (2-20). Seven patients achieved a partial response (PR) for an overall response rate of 17.9%. A total of 29 (74.4%) patients had stable disease (SD) for a DCR of 92.3%. With a median follow up 7,5 months, median PFS was 7.58 months (95% CI 6.6-8.5) and the median OS has not yet been reached. Median duration of PR response was 8,7 months (4,11-10,94+) and median duration of SD was 4,14 months (1,84-11,99+). The main treatment-related grade 3 or 4 adverse events were neutropenia (7/38; 18.4%), anemia (1/38; 2.6%) and diarrhea (2/38; 4.3%).The most frequent adverse events of special interest (AESIs) any grade were hypertension (16/38; 42.1%), bleeding/hemorrhage (10/38; 26.3%), proteinuria (6/38; 15.7%) and venous thromboembolic events (10/38; 26,3%). Gastrointestinal perforation developed in two patients (2/38; 5.3%). No treatment-related deaths occurred. Conclusion: In our research ramucirumab with irinotecan and fluoropyrimidines demonstrate the high activity and a manageable safety profile in patients with pre-treated metastatic GC.

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