medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2017-14-30-38medsovet-2180Research ArticleТАРГЕТНАЯ ТЕРАПИЯ ОПУХОЛЕЙTarget therapy of tumorsПРИМЕНЕНИЕ РАМУЦИРУМАБА В ЛЕЧЕНИИ БОЛЬНЫХ ДИССЕМИНИРОВАННОЙ АДЕНОКАРЦИНОМОЙ ЖЕЛУДКА В РЕАЛЬНОЙ КЛИНИЧЕСКОЙ ПРАКТИКЕ ПРЕДВАРИТЕЛЬНЫЙ АНАЛИЗ ОПЫТА НАЦИОНАЛЬНОГО МЕДИЦИНСКОГО ИССЛЕДОВАТЕЛЬСКОГО ЦЕНТРА ОНКОЛОГИИ ИМ. Н.Н. БЛОХИНАREAL-LIFE CLINICAL UTILITY OF RAMUCIRUMAB FOR THE TREATMENT OF PATIENTS WITH DISSEMINATED GASTRIC ADENOCARCINOMA: PRELIMINARY REVIEW OF THE EXPERIENCE OF BLOKHIN RUSSIAN CANCER RESEARCH CENTREБесоваН. С.BesovaN. S.

Кандидат медицинских наук.

Москва

PhD in medicine.

Moscow

ТитоваТ. А.TitovaT. A.

Москва

Moscow

ГорбуноваВ. А.GorbunovaV. A.

Доктор медицинских наук,  профессор.

Москва

MD, Prof.

Moscow

ГордееваО. О.GordeevaO. O.

Москва

Moscow

ТрякинА. А.TryakinA. A.

Доктор медицинских наук.

Москва

MD.

Moscow

СнеговойА. В.SnegovoyA. V.

Доктор медицинских наук.

Москва

MD.

Moscow

НасыроваР. Ю.NasyrovaR. Yu.

Кандидат медицинских наук.

Москва

PhD in medicine.

Moscow

РумянцевА. А.RumyantsevA. A.

Москва

Moscow

ВорошиловаЕ. А.VoroshilovaE. A.

Кандидат медицинских наук.

Москва

PhD in medicine.

Moscow

АртамоноваЕ. В.ArtamonovaE. V.

Доктор медицинских наук.

Москва

MD.

Moscow

Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина Минздрава РоссииРоссияBlokhin Russian Cancer Research Centre, Ministry of HealthRussian Federation2017141120170143038Copyright © Бесова Н.С., Титова Т.А., Горбунова В.А., Гордеева О.О., Трякин А.А., Снеговой А.В., Насырова Р.Ю., Румянцев А.А., Ворошилова Е.А., Артамонова Е.В., 20172017Бесова Н.С., Титова Т.А., Горбунова В.А., Гордеева О.О., Трякин А.А., Снеговой А.В., Насырова Р.Ю., Румянцев А.А., Ворошилова Е.А., Артамонова Е.В.Besova N.S., Titova T.A., Gorbunova V.A., Gordeeva O.O., Tryakin A.A., Snegovoy A.V., Nasyrova R.Y., Rumyantsev A.A., Voroshilova E.A., Artamonova E.V.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/2180

Ангиогенез является важной мишенью, а антиангиогенные препараты – перспективным направлением противоопу- холевой терапии. Рамуцирумаб – антиангиогенный препарат, являющийся антителом к рецепторам фактора роста эндотелия сосудов 2-го типа (VEGFR-2). В апреле 2014  г. на основании результатов исследований REGARD и RAINBOW препарат был рекомендован  FDA в качестве второй линии лечения больных диссеминированным раком желудка (РЖ) в монорежиме или в комбинации с паклитакселом.

В статье представлены результаты применения рамуцирумаба во 2-й линии лечения больных диссеминированным РЖ. С апреля 2017  г. по 20.09.17 г. в ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России лечение рамуци- рубамом было проведено  40 больным: в монорежиме – 8 больным, в комбинации с паклитакселом – 26.

Медиана выживаемости без  прогрессирования процесса (МВБП) и медиана общей выживаемости (МОВ) больных на монотерапии составили 1,8  и 7,6  мес. соответственно, для комбинации рамуцирумаба с паклитакселом МВБП составила 5,02  мес., МОВ не достигнута. Переносимость лечения была удовлетворительной. Полученные данные сопоставимы с результатами международных исследований REGARD и RAINBOW.

Angiogenesis   has  become  an  important  target  in  the  treatment  of  solid  tumors  and  anti-angiogenic   agents   are a  promising  approach  to  cancer  therapy.  Ramucirumab, an  anti-angiogenic   agent   specifically  targeting  vascular endothelial  growth factor receptor-2  (VEGFR-2). In April 2014, the FDA approved ramucirumab as a single  agent  or in combination with paclitaxel  for treatment of advanced gastric or gastroesophageal junction adenocarcinoma (GC) that has progressed on or after prior fluoropyrimidine – or platinumcontaining chemotherapy based on data of REGARD and RAINBOW trials.

We evaluated the progression free (PFS), overall survival (OS) and safety of ramucirumab in patients (pts) with advanced GC in routine clinical practice From June 2016  to 20 Sep 2017  40 pts with advanced GC were treated with ramucirumab in the second line treatment as single  agent (8 pts) or in combination with paclitaxel  (26 pts) in N.N.Blokhin National medical research center of oncology.

Median PFS (MPFS) and median OS (MOS) was 1,8  and 7,6 mons for monotherapy group. For combination group MPFS was 5,02  mons, MOS was not reached. Ramucirumab had an acceptable safety profile Our data are similar to the data of REGARD and RAINBOW trials.

диссеминированный рак желудкавторая линия лечениярамуцирумабadvanced gastric cancersecond line treatmentramucirumabReferencesTorre LA, Bray F, Siegel RL, Ferlay J, LortetTieulent J, Jemal A. Global cancer statistics, 2012. CA: A Cancer Journal for Clinicians, 2015, 65(Issue 2): fmi–fmii, 83–162. DOI: 10.3322/caac.21262.Torre LA, Bray F, Siegel RL, Ferlay J, LortetTieulent J, Jemal A. Global cancer statistics, 2012. CA: A Cancer Journal for Clinicians, 2015, 65(Issue 2): fmi–fmii, 83–162. DOI: 10.3322/caac.21262.Злокачественные заболевания в России в 2015 году (заболеваемость и смертность). Под ред. Каприна А.Д., Старинского В.В., Петровой Г.В. МНИОИ П.А. Герцена – филиал ФГБУ «НМИРЦ» Минздрава России. М., 2017.Злокачественные заболевания в России в 2015 году (заболеваемость и смертность). Под ред. Каприна А.Д., Старинского В.В., Петровой Г.В. МНИОИ П.А. Герцена – филиал ФГБУ «НМИРЦ» Минздрава России. М., 2017.Состояние онкологической помощи населению России в 2016 году. Под ред. Каприна А.Д., Старинского В.В., Петровой Г.В. МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИРЦ» Минздрава России, М., 2017 г.Состояние онкологической помощи населению России в 2016 году. Под ред. Каприна А.Д., Старинского В.В., Петровой Г.В. МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИРЦ» Минздрава России, М., 2017 г.Bang Y-J, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastrooesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet, 2010, 376: 687–97.Bang Y-J, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastrooesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet, 2010, 376: 687–97.Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med, 2008, 358: 36–46.Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med, 2008, 358: 36–46.Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol, 2008, 9: 215–21.Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol, 2008, 9: 215–21.Iacovelli R, Pietrantonio F, Farcomeni A, Maggi C, Palazzo A, et al. Chemotherapy or Targeted Therapy as Second-Line Treatment of Advanced Gastric Cancer. A Systematic Review and MetaAnalysis of Published Studies. PLoS ONE, 20149(9): e108940. doi:10.1371/journal.pone.0108940.Iacovelli R, Pietrantonio F, Farcomeni A, Maggi C, Palazzo A, et al. Chemotherapy or Targeted Therapy as Second-Line Treatment of Advanced Gastric Cancer. A Systematic Review and MetaAnalysis of Published Studies. PLoS ONE, 20149(9): e108940. doi:10.1371/journal.pone.0108940.Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer– a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer, 2011, 47: 2306-2314. [PMID: 21742485 DOI:10.1016/j.ejca.2011.06.002].Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer– a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer, 2011, 47: 2306-2314. [PMID: 21742485 DOI:10.1016/j.ejca.2011.06.002].Ford H, Marshall A, Wadsley J, Coxon FY, et al. Cougar-02: A randomized phase III study of docetaxel versus active symptom control in Lancet Oncol, 2014, 15: 78–86. [PMID: 24332238 DOI: 10.1016/S14702045(13)705497].Ford H, Marshall A, Wadsley J, Coxon FY, et al. Cougar-02: A randomized phase III study of docetaxel versus active symptom control in Lancet Oncol, 2014, 15: 78–86. [PMID: 24332238 DOI: 10.1016/S14702045(13)705497].Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol, 2012, 30: 1513-1518. [PMID: 22412140 DOI: 10.1200/JCO.2011.39.4585]Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol, 2012, 30: 1513-1518. [PMID: 22412140 DOI: 10.1200/JCO.2011.39.4585]Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, et al. Randomized, open-label,phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 Trial. J. Clin. Oncol., 2013, 31(35): 4438–4444. [PMID: 24190112 DOI: 10.1200/JCO.2012.48.5805].Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, et al. Randomized, open-label,phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 Trial. J. Clin. Oncol., 2013, 31(35): 4438–4444. [PMID: 24190112 DOI: 10.1200/JCO.2012.48.5805].Galdy S, Cella CA, Spada F, Murgioni S, Frezza AM, Ravenda SP, Zampino MG, Fazio N, et al. Systemic therapy beyond first-line in advanced gastric cancer: An overview of the main randomized clinical trials. Crit Rev Oncol/Hematol, 2015. http://dx.doi.org/10.1016/j.critrevonc.2015.09.004Galdy S, Cella CA, Spada F, Murgioni S, Frezza AM, Ravenda SP, Zampino MG, Fazio N, et al. Systemic therapy beyond first-line in advanced gastric cancer: An overview of the main randomized clinical trials. Crit Rev Oncol/Hematol, 2015. http://dx.doi.org/10.1016/j.critrevonc.2015.09.004Tian S, Quan H, Xie C, Guo H, Lü F, Xu Y et al. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci., 2011, 102(7): 1374-80.Tian S, Quan H, Xie C, Guo H, Lü F, Xu Y et al. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci., 2011, 102(7): 1374-80.Spratlin JL, Cohen RB, Eadens M, Gore L, Camidge DR, Diab S et al. Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J. Clin. Oncol., 2010, 28(5): 780-7.Spratlin JL, Cohen RB, Eadens M, Gore L, Camidge DR, Diab S et al. Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J. Clin. Oncol., 2010, 28(5): 780-7.Lu D et al. Tailoring in vitro selection for a picomolar affinity human antibody directed against vascular endothelial growth factor receptor 2 for enhanced neutralizing activity. J Biol Chem, 2003, 278(44): 43496–43507.Lu D et al. Tailoring in vitro selection for a picomolar affinity human antibody directed against vascular endothelial growth factor receptor 2 for enhanced neutralizing activity. J Biol Chem, 2003, 278(44): 43496–43507.Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J. ed advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet, 2014, 383: 31-39. [PMID: 24094768 DOI: 10.1016/S0140-6736(13)61719-5].Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J. ed advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet, 2014, 383: 31-39. [PMID: 24094768 DOI: 10.1016/S0140-6736(13)61719-5].Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastrooesophageal junction adenocarcinoma (RAINBOW): a doubleblind, randomised phase 3 trial. Lancet Oncol, 2014, 15: 1224-1235. [PMID:25240821 DOI: 10.1016/S1470-2045(14)70420-6].Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastrooesophageal junction adenocarcinoma (RAINBOW): a doubleblind, randomised phase 3 trial. Lancet Oncol, 2014, 15: 1224-1235. [PMID:25240821 DOI: 10.1016/S1470-2045(14)70420-6].Young K, Smyth E and Chau I. Ramucirumab for advanced gastric cancer or gastro-oesophageal junction adenocarcinoma. Ther Adv Gastroenterol, 2015, 8(6): 373-383. DOI: 10.1177/1756283X15592586.Young K, Smyth E and Chau I. Ramucirumab for advanced gastric cancer or gastro-oesophageal junction adenocarcinoma. Ther Adv Gastroenterol, 2015, 8(6): 373-383. DOI: 10.1177/1756283X15592586.Cancer Therapy Evaluation Program. Common terminology criteria for adverse events v4.02. 2009.[http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40 (accessed Sept 15, 2009)].Cancer Therapy Evaluation Program. Common terminology criteria for adverse events v4.02. 2009.[http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40 (accessed Sept 15, 2009)].Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst, 2000, 92: 205–16.Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst, 2000, 92: 205–16.Fuchs CS, Muro K, Tomasek J, Van Cutsem E, Cho JY, Oh S-C, Safran H, Bodoky G, Chau I, Shimada Y, Al-Batran S-E, Passalacqua R, Ohtsu A, Emig M, Ferry D, Chandrawansa K, Hsu Y, Sashegyi A, Liepa AM, Wilke H. Prognostic Factor Analysis of Overall Survival in Gastric Cancer from Two Phase III Studies of Second-line Ramucirumab (REGARD and RAINBOW) Using Pooled Patient Data. J Gastric Cancer, 2017 Jun, 17(2): 132-144. [https://doi.org/10.5230/jgc.2017.17.e16pISSNFuchs CS, Muro K, Tomasek J, Van Cutsem E, Cho JY, Oh S-C, Safran H, Bodoky G, Chau I, Shimada Y, Al-Batran S-E, Passalacqua R, Ohtsu A, Emig M, Ferry D, Chandrawansa K, Hsu Y, Sashegyi A, Liepa AM, Wilke H. Prognostic Factor Analysis of Overall Survival in Gastric Cancer from Two Phase III Studies of Second-line Ramucirumab (REGARD and RAINBOW) Using Pooled Patient Data. J Gastric Cancer, 2017 Jun, 17(2): 132-144. [https://doi.org/10.5230/jgc.2017.17.e16pISSN

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