Пятилетняя общая выживаемость больных метастатическим раком почки, получавших эверолимус при прогрессировании на фоне лечения бевацизумабом: проспективное многоцентровое исследование CRAD001LRU02T

Background. In a CRAD001LRU02T study of everolimus for metastatic renal cell carcinoma patients previously treated with bevacizumab ±  interferon, median overall survival (OS) was 17.4 months (95 % confidence interval 13.5–21.3 month).Objective of final analysis was to evaluate 5-year OS and long-term toxicity in this study.Materials and methods. Survival data were collected from 37 patients with bevacizumab-refractory metastatic renal cell carcinoma who received everolimus in a completed prospective multicenter study. Patients were predominantly male, 89 % had ECOG performance status of 0/1, 51 % received previous bevacizumab in combination with interferon, and 38/62% had MSKCC favorable/intermediate risk disease.Results. The 5-year survival rate was 16.2% (95 % confidence interval 14.1–18.3 %), with a median follow-up of 5 years. The 1-, and 3-year OS rates were 81.0 and 43.0 %, respectively. The median duration of second-line of everolimus was 315 (range 61–569) days. 11 (29.7 %) patients received third-line therapy with a median duration of 3.6 months. Confirmed objective tumor responses were seen in 5 (14.0 %) patients. 70.0 % (n = 26) patients had a stable disease. 1 (2.7 %) patient achieved complete response after 4 years of therapy. One (2.7 %) patient  discontinued everolimus therapy on their own accord due to relapse of systemic lupus erythematosus and one (2.7 %)  patient had 14-days interruption of an everolimus therapy due to grade 3 hyperglycemia. No grade 4 treatment-related toxicity was found.Conclusions. Everolimus provided an estimated 5-year survival rate of 16.2 % for bevacizumab-resistant metastatic renal cell carcinoma. Prolonged everolimus was not associated with new types or increased severity of adverse events.Введение. В исследовании CRAD001LRU02T эффективности эверолимуса у больных метастатическим почечно-клеточным раком, получавших ранее терапию бевацизумабом в комбинации с интерфероном или без него, медиана общей выживаемости (ОВ) составила 17,4 мес (95 % доверительный интервал 13,5–21,3 мес).Цель работы – оценка 5-летней ОВ и отдаленной токсичности в этом исследовании.Материалы и методы. Данные по ОВ были получены у 37 пациентов, рефрактерных к терапии бевацизумабом и получивших эверолимус в рамках проспективного многоцентрового исследования. Большинство пациентов – мужчины, 89 % больных имели статус по шкале ECOG 0 / 1, 51 % пациентов получили предшествующую терапию бевацизумабом в комбинации с интерфероном. Благоприятный прогноз имели 38 % больных, промежуточный – 62 %.Результаты. При медиане наблюдения 5 лет 5-летняя ОВ составила 16,2 % (95 % доверительный интервал 14,1–18,3 %),  1- и 3-летняя ОВ – 81,0 и 43,0 % соответственно. Медиана продолжительности 2-й линии терапии эверолимусом составила 315 (61–569) сут. С медианой длительности 3,6 мес 3-ю линию терапии получили 11 (29,7 %) пациентов. Подтвержденные объективные ответы отмечены у 5 (14,0 %) больных. Стабилизация болезни наблюдалась у 70,0 % (n = 26) пациентов. Полного ответа спустя 4 года терапии достиг 1 (2,7 %) пациент. Из-за обострения системной красной волчанки 1 (2,7 %) больной по собственному желанию прекратил терапию эверолимусом и 1 (2,7 %) пациент имел перерыв в лечении в течение 14 сут в связи с развитием гипергликемии III степени токсичности. Нежелательных явлений IV степени тяжести не выявлено.Заключение. Терапия эверолимусом привела к 5-летней ОВ 16,2 % у больных метастатическим почечно-клеточным раком, ранее резистентных к терапии бевацизумабом. Длительная терапия эверолимусом не была ассоциирована с новыми видами выраженной токсичности или повышением частоты нежелательных явлений

Five-year overall survival of metastatic renal cell carcinoma patients treated with everolimus after progression on bevacizumab: a prospective multicenter study CRAD001LRU02T

Background. In a CRAD001LRU02T study of everolimus for metastatic renal cell carcinoma patients previously treated with bevacizumab ±  interferon, median overall survival (OS) was 17.4 months (95 % confidence interval 13.5–21.3 month).Objective of final analysis was to evaluate 5-year OS and long-term toxicity in this study.Materials and methods. Survival data were collected from 37 patients with bevacizumab-refractory metastatic renal cell carcinoma who received everolimus in a completed prospective multicenter study. Patients were predominantly male, 89 % had ECOG performance status of 0/1, 51 % received previous bevacizumab in combination with interferon, and 38/62% had MSKCC favorable/intermediate risk disease.Results. The 5-year survival rate was 16.2% (95 % confidence interval 14.1–18.3 %), with a median follow-up of 5 years. The 1-, and 3-year OS rates were 81.0 and 43.0 %, respectively. The median duration of second-line of everolimus was 315 (range 61–569) days. 11 (29.7 %) patients received third-line therapy with a median duration of 3.6 months. Confirmed objective tumor responses were seen in 5 (14.0 %) patients. 70.0 % (n = 26) patients had a stable disease. 1 (2.7 %) patient achieved complete response after 4 years of therapy. One (2.7 %) patient  discontinued everolimus therapy on their own accord due to relapse of systemic lupus erythematosus and one (2.7 %)  patient had 14-days interruption of an everolimus therapy due to grade 3 hyperglycemia. No grade 4 treatment-related toxicity was found.Conclusions. Everolimus provided an estimated 5-year survival rate of 16.2 % for bevacizumab-resistant metastatic renal cell carcinoma. Prolonged everolimus was not associated with new types or increased severity of adverse events