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Analysis of prognostic factors for survival in the Russian population of patients with disseminated gastric cancer, who received ramucirumab as secondline therapy in the RAMSELGA trial

https://doi.org/10.21518/2079-701X-2020-9-165-174

Abstract

Background. Ramucirumab is a monoclonal antibody that inhibits the vascular endothelial growth factor receptor-2 (VEGFR2). The study is aimed to analyse prognostic factors for survival in patients with disseminated gastric cancer who received ramucirumab in the second-line therapy in ’real-life’ clinical setting of Russia (RAMSELGA).
Methods. We retrospectively analysed the outcome of 163 patients aged 20–78 years from 11 oncological centres in Russia. Survival analysis was performed using the Kaplan – Meier model, and regression analysis was performed using the Cox model.
Results. In a univariate analysis of overall survival, 5 factors were identified as independent factors of an unfavourable prognosis: 1) age <65 years (RR 0.542; 95% CI 0.302–0.971; p = 0.039); 2) time to tumour progression on the first-line therapy is not more than four months. (RR 0.161; 95% CI 0.105–0.246; p = 0.0000); 3) a low grade tumour or colloid cancer (RR 1,868; 95% CI 1,063–3,284; p = 0,030); 4) peritoneal metastasis (RR 1.549; 95% CI 1.026–2.339; p = 0.037); 5) ascites or pleurisy (RR 0.624; 95% CI 0.424–0.920; p = 0.017). In a multivariate analysis, favourable prognostic factors of overall survival of patients included age – 65 years or older (OS 2.288; 95% CI 1.240–4.220; p = 0.008) and time to tumour progression on the first-line therapy – more than 4 months (OS 6.650; 95% CI 4.221–10.477; p = 0.000).
Conclusion. Despite an active search, prognostic factors for survival in patients that are universal for dGC have not yet been found. To build a universal prognostic model, a very thoughtful analysis considering not only clinical and laboratory, but also pathomorphological and molecular genetic characteristics is required.

About the Authors

N. S. Besova
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

Natalia S. Besova, Cand. of Sci. (Med.), Lead Researcher, Cancer Drug Therapy Department (Chemotherapeutic No. 1), N.N. Trapeznikov Research Institute of Clinical Oncology

24, Kashirskoye Shosse, Moscow, 115478



T. A. Titova
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

Tatyana A. Titova, Oncologist, Cancer Drug Therapy Department (Chemotherapeutic No. 1), N.N. Trapeznikov Research Institute of Clinical Oncology

24, Kashirskoye Shosse, Moscow, 115478



Е. V. Artamonova
N.N. Blokhin National Medical Research Center of Oncology; Pirogov Russian National Research Medical University
Russian Federation

Elena V. Artamonova, Dr. of Sci. (Med.), Head of Cancer Drug Therapy Department (Chemotherapeutic No. 1), N.N. Trapeznikov Research Institute of Clinical Oncology; Professor, Chair for Oncology and X-ray Therapy, General Medicine Faculty

Scopus Author ID: 6603662138

24, Kashirskoye Shosse, Moscow, 115478 

1, Ostrovityanov St., Moscow, 117997



A. A. Tryakin
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

Alexey А. Tryakin, Dr. of Sci. (Med.), Chief Researcher, Cancer Drug Therapy Department (Chemotherapeutic No. 2), N. N. Trapeznikov Research Institute of Clinical Oncology

Scopus Author ID: 26027590600

24, Kashirskoye Shosse, Moscow, 115478



D. L. Stroyakovskiy
Moscow City Oncology Hospital No. 62
Russian Federation

Daniil L. Stroyakovskii, Cand. of Sci. (Med.), Head of Chemotherapeutic Department

27, Bldg. 1-26, Istra Town, p/o Stepanovskoe, Krasnogorsky District, Moscow Region, 143423



E. V. Perminova
Moscow City Oncology Hospital No. 62
Russian Federation

Evgeniya V. Perminova, Oncologist, Chemotherapeutic Department

27, Bldg. 1-26, Istra Town, p/o Stepanovskoe, Krasnogorsky District, Moscow Region, 143423



D. Yu. Yukalchuk
Irkutsk Regional Cancer Centre
Russian Federation

Denis Yu. Iukalchuk, Cand. of Sci. (Med.), Chemotherapeutic Department

32, Frunze St., Irkutsk, 664035



D. M. Ponomarenko
Irkutsk Regional Cancer Centre
Russian Federation

Dmitriy M. Ponomarenko, Cand. of Sci. (Med.), Head of Chemotherapeutic Department

32, Frunze St., Irkutsk, 664035



N. P. Belyak
City Clinical Oncology Centre
Russian Federation

Natalya P. Beliak, Cand. of Sci. (Med.), Oncologist, Chemotherapy Department

3/5, 2nd Berezovaya Alleya, St Petersburg, 197022



R. V. Orlova
City Clinical Oncology Centre; St Petersburg University
Russian Federation

Rashida V. Orlova, Dr. of Sci. (Med.), Professor, Head of Chair for Oncology; Head of Specialized Oncology Centre, Chief Oncologist of Clinical Hospital No. 22, Scientific Advisor on Antitumor Drug Therapy  

3/5, 2nd Berezovaya Alleya, St Petersburg, 197022

7/9, Universitetskaya Nab., St Petersburg, 199034



G. M. Teletaeva
Petrov National Medical Cancer Research Centre
Russian Federation

Gulfiya M. Teletaeva, Cand. of Sci. (Med.), Oncologist, Researcher

68, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758



E. Yu. Ratner
Republican Oncological Clinical Dispensary of the Ministry of Health of the Republic of Tatarstan
Russian Federation

Ekaterina Yu. Ratner, Oncologist, Chemotherapy Department No. 1

29, Sibirskiy Trakt St., Kazan, Republic of Tatarstan, 420029



A. S. Mochalova
Medsi Group
Russian Federation

Anastasiia S. Mochalova, Cand. of Sci. (Med.), Oncologist

71, Tamanskaya St., Serebryanyy Bor, Moscow, 123103



O. O. Gordeeva
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

Olga O. Gordeeva, Physician, Department of Chemotherapy and Multimodal Treatment of Malignant Tumours, third-year postgraduate student, N.N. Trapeznikov Research Institute of Clinical Oncology

24, Kashirskoye Shosse, Moscow, 115478



A. S. Zhabina
Petrov National Medical Cancer Research Centre
Russian Federation

Albina S. Zhabina, Cand. of Sci. (Med.), Oncologist, Department of Biotherapy, Clinical Scientific and Practical Centre for Specialized Medical Care (Oncology), Researcher, Department of Innovative Technology and Rehabilitation

68, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758



S. V. Gamayunov
A.F. Tsyb Medical Radiological Research Centre
Russian Federation

Sergey V. Gamayunov, Cand. of Sci. (Med.), Senior Researcher, Department of Radiation Injuries

Scopus Author ID: 55562003600; Researcher ID: E-4857-2014

4, Koroleva St., Obninsk, Kaluga Region, 249036



A. V. Smolin
Main Military Clinical Hospital named after Academician N.N. Burdenko
Russian Federation

Alexey V. Smolin, Cand. of Sci. (Med.), Oncologist, Head of Radiological Centre, Chief Radiologist

3, Gospitalnaya Square, Moscow, 105094



A. Yu. Povyshev
Regional Clinical Hospital
Russian Federation

Anton Yu. Povyshev, Oncologist, Department of Chemotherapy and Oncohematology

40, Kalinina St., Khanty-Mansiysk, 628012



M. I. Andrievskikh
Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine
Russian Federation

Maria I. Andrievskikh, Oncologist

42, Blyukher St., Chelyabinsk, 454087



I. S. Stilidi
N.N. Blokhin National Medical Research Center of Oncology; Pirogov Russian National Research Medical University; Russian Medical Academy of Continuous Professional Education
Russian Federation

Ivan S. Stilidi, member of the Russian Academy of Sciences, Dr. of Sci. (Med.), Professor, Director; Head of Chair for Oncology and X-ray Therapy, General Medicine Department; Professor, Chair for Oncology and Palliative Medicine, Department of Surgery

Scopus Author ID: 6602949492

24, Kashirskoye Shosse, Moscow, 115478 

1, Ostrovityanov St., Moscow, 117997

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993



References

1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians. 2018;68(6):394–424. doi: 10.3322/caac.21492.

2. Каприн А.Д., Старинский В.В., Петрова Г.В. (ред.) Злокачественные новообразования в России в 2017 году (заболеваемость и смертность). М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России; 2018. 250 с. Режим доступа: https://glavonco.ru/upload/pages/cancer-register/statistika_zabol_2017.pdf. Kaprin A.D., Starinskiy V.V., Petrova G.V. (eds.) Cancer statistics in Russia in 2017. Moscow: Gertsen P.A. Moscow Cancer Research Institute – filial of TSYB Medical Radiological Research Center of the Ministry of Health of Russia; 2018. 250 p. (In Russ.) Available at: https://glavonco.ru/upload/pages/cancer-register/statistika_zabol_2017.pdf.

3. Каприн А.Д., Старинский В.В., Петрова Г.В. (ред.) Состояние онкологической помощи населению России в 2018 году. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России; 2019. 263 с. Режим доступа: https://nnood.ru/wp-content/uploads/2019/04/ Statichticheskijj-ezhegodnik-Gercena-2018.pdf. Kaprin A.D., Starinskiy V.V., Petrova G.V. (eds.) State of Cancer Care in Russia in 2018. Moscow: Gertsen P.A. Moscow Cancer Research Institute – filial of TSYB Medical Radiological Research Center of the Ministry of Health of Russia; 2019. 263 p. (In Russ.) Available at: https://nnood.ru/wp-content/uploads/2019/04/Statichticheskijj-ezhegodnik-Gercena-2018.pdf.

4. Vanhoefer U., Rougier P., Wilke H., Ducreux M.P., Lacave A.J., Van Cutsem E. et al. Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol. 2000;18(14):2648–2657. doi: 10.1200/JCO.2000.18.14.2648.

5. Kang Y., Kang W.K., Shin D.B., Chen J., Xiong J., Wang J. et al. Capecitabine/ cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Annals of Oncology. 2009;20(4):666–673. doi: 10.1093/annonc/mdn717.

6. Al-Batran S.-E., Hartmann J.T., Probst S., Schmalenberg H., Hollerbach S., Hofheinz R. et al. Phase III Trial in Metastatic Gastroesophageal Adenocarcinoma with Fluorouracil, Leucovorin Plus Either Oxaliplatin or Cisplatin: A Study of the Arbeitsgemeinschaft Internistische Onkologie. Journal of Clinical Oncology. 2008;26(9):1435–1442. doi: 10.1200/JCO.2007.13.9378.

7. Park Y.H., Kim B.S., Ryoo B.Y., Yang S.H. A phase II study of capecitabine plus 3-weekly oxaliplatin as first-line therapy for patients with advanced gastric cancer. Br J Cancer. 2006;94(7):959–963. doi: 10.1038/sj.bjc.6603046.

8. Dank M., Zaluski J., Barone C., Valvere V., Yalcin S., Peschel C. et al. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Annals of Oncology. 2008;19(8):1450–1457. doi: 10.1093/annonc/mdn166.

9. Guimbaud R., Louvet C., Ries P., Ychou M., Maillard E., André T. et al. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study. J Clin Oncol. 2014;32(31):3520–3526. doi: 10.1200/JCO.2013.54.1011.

10. Van Cutsem E., Moiseyenko V.M., Tjulandin S., Majlis A., Constenla M., Boni C. et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2016;24(31):4991–4997. doi: 10.1200/JCO.2006.06.8429.

11. Shah M.A., Janjigian Y.Y., Stoller R., Shibata S., Kemeny M., Krishnamurthi S. et al. Randomized Multicenter Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil (DCF) Versus DCF Plus Growth Factor Support in Patients With Metastatic Gastric Adenocarcinoma: A Study of the US Gastric Cancer Consortium. J Clin Oncol. 2015;33(33):3874–3879. doi: 10.1200/JCO.2015.60.7465.

12. Al-Batran S.-E., Hartmann J.T., Hofheinz R., Pauligk C., Atmaca A., Jägeret E. et al. Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Annals of Oncology. 2008;19(11):1882–1887. doi: 10.1093/annonc/mdn403.

13. Cunningham D., Starling N., Rao S., Iveson T., Nicolson M., Coxon F. et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358:36–46. doi: 10.1056/NEJMoa073149.

14. Koizumi W., Narahara H., Hara T., Takagane A., Akiya T., Takagi M. 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(3):215–221. doi: 10.1016/S1470-2045(08)70035-4.

15. Iacovelli R., Pietrantonio F., Farcomeni A., Maggi C., Palazzo A., Ricchini F. et al. Chemotherapy or Targeted Therapy as Second-Line Treatment of Advanced Gastric Cancer. A Systematic Review and Meta-Analysis of Published Studies. PLoS ONE. 2014;9(9):e108940. doi: 10.1371/journal.pone.0108940.

16. Thuss-Patience P.C., Kretzschmar A., Bichev D., Deist T., Hinke A., Breithaupt K. et al. 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(15):2306–2314. doi: 10.1016/j.ejca.2011.06.002.

17. Ford H., Marshall A., Bridgewater J.A., Janowitz T., Coxon F.Y., Wadsley J. et al. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014;15(1):78–86. doi: 10.1016/S1470-2045(13)70549-7.

18. Kang J.H., Lee S.I., Lim do H., Park K.W., Oh S.Y., Kwon H.C. et al. 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(13):1513–1518. doi: 10.1200/JCO.2011.39.4585.

19. 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. doi: 10.1200/JCO.2012.48.5805.

20. Fuchs C.S., Tomasek J., Yong C.J., Dumitru F., Passalacqua R., Goswami C. et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31–39. doi: 10.1016/S0140-6736(13)61719-5.

21. Wilke H., Muro K., Van Cutsem E., Oh S.C., Bodoky G., Shimada Y. et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastrooesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15(11):1224-1235. doi: 10.1016/S1470-2045(14)70420-6.

22. Di Bartolomeo M., Niger M., Tirino G., Petrillo A., Berenato R., Laterza M.M. et al. Ramucirumab as Second-Line Therapy in Metastatic Gastric Cancer: Real-World Data from the RAMoss Study. Targeted Oncology. 2018;13:(2):227–234. doi: 10.1007/s11523-018-0562-5.

23. Klempner S.J., Maron S.B., Chase K., Lomnicki S., Wainberg Z.A., Catenacci D.V.T. Initial Report of Second-Line FOLFIRI in Combination with Ramucirumab in Advanced Gastroesophageal Adenocarcinomas: A Multi-Institutional Retrospective Analysis. The Oncologist. 2018;23:1–8. Available at: https://sci-hub.st/10.1634/theoncologist.2018-0602.

24. Fuchs C.S., Muro K., Tomasek J., Van Cutsem E., Cho J.Y., Oh S-C. et al. 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;17(2):132–144. doi: 10.5230/jgc.2017.17.e16.

25. Therasse P., Arbuck S.G., Eisenhauer E.A., Wanders J., Kaplan R.S., Rubinstein L. et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst. 2000;92(3):205–216. doi: 10.1093/jnci/92.3.205.

26. Klempner S.J., Wainberg Z.A., Muro K., Chao J., Catenacci D.V.T., Ajani J.A. et al. Impact of frontline doublet versus triplet therapy on clinical outcomes: Exploratory analysis from the RAINBOW study. J Clin Oncol. 2020;38(15):4543. doi: 10.1200/JCO.2020.38.15_suppl.4543.

27. Catalano V., Graziano F., Santini D., D’Emidio S., Baldelli A.M., Rossi D. et al. Second-line chemotherapy for patients with advanced gastric cancer: who may benefit? Br J Cancer. 2008;99(9):1402–1407. doi: 10.1038/sj.bjc.6604732.

28. Kanagavel D., Pokataev I.A., Fedyanin M.Y., Tryakin A.A., Bazin I.S., Narimanov M.N. et al. A prognostic model in patients treated for metastatic gastric cancer with second-line chemotherapy. Ann Oncol. 2010;21(9):1779–1785. doi: 10.1093/annonc/mdq032.

29. Chau I., Norman A.R., Cunningham D., Waters J.S., Oates J., Ross P.J. Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer – pooled analysis from three multicenter, randomized, controlled trials using individual patient data. J Clin Oncol. 2004;22(12):2395–2403. doi: 10.1200/jco.2004.08.154.

30. Koo D.H., Ryoo B.Y., Kim H.J., Ryu M.H., Lee S.S., Moon J.H. et al. A prognostic model in patients who receive chemotherapy for metastatic or recurrent gastric cancer: validation and comparison with previous models. Cancer Chemother Pharmacol. 2011;68:913–921. doi: 10.1007/s00280-011-1561-8.

31. Takahari D., Boku N., Mizusawa J., Takashima A., Yamada Y., Yoshino T. et al. Determination of prognostic factors in Japanese patients with advanced gastric cancer using the data from a randomized controlled trial, Japan clinical oncology group 9912. The Oncologist. 2014;19(4):358–366. doi: 10.1634/theoncologist.2013-0306.


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For citations:


Besova NS, Titova TA, Artamonova ЕV, Tryakin AA, Stroyakovskiy DL, Perminova EV, Yukalchuk DY, Ponomarenko DM, Belyak NP, Orlova RV, Teletaeva GM, Ratner EY, Mochalova AS, Gordeeva OO, Zhabina AS, Gamayunov SV, Smolin AV, Povyshev AY, Andrievskikh MI, Stilidi IS. Analysis of prognostic factors for survival in the Russian population of patients with disseminated gastric cancer, who received ramucirumab as secondline therapy in the RAMSELGA trial. Meditsinskiy sovet = Medical Council. 2020;(9):165-174. (In Russ.) https://doi.org/10.21518/2079-701X-2020-9-165-174

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ISSN 2079-701X (Print)
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