Efficacy of ramucirumab in the second-line treatment of patients with disseminated gastric cancer in routine clinical practice in Russia (RAMSELGA observational study)

Capa

Citar

Texto integral

Acesso aberto Acesso aberto
Acesso é fechado Acesso está concedido
Acesso é fechado Acesso é pago ou somente para assinantes

Resumo

Background. Currently, ramucirumab, an inhibitor of type 2 vascular endothelial growth factor receptors, in combination with paclitaxel is the most effective second-line treatment regimen for disseminated gastric cancer (DGC). The experience of successful use of ramucirumab in real clinical practice in various countries of the world is widely presented in the literature.

Objective. Evaluation of the effectiveness of ramucirumab as monotherapy or in combination with chemotherapy as a second-line treatment for patients with DGC in routine clinical practice in Russia.

Methods. The analysis included data from 163 patients with GC from 11 oncology institutions in Russia who received ramucirumab as part of the second-line treatment: 17 patients were prescribed ramucirumab as a monotherapy, 104 – in combination with paclitaxel, 42 – in combination with irinotecan-based regimens. The treatment efficacy was assessed.

Results. The efficacy of ramucirumab as a monotherapy was: disease stabilization – 47.1%, median progression-free survival (mPFS) – 2.2 months, median overall survival (mOS) – 5.6 months. When treating with ramucirumab in combination with paclitaxel, the objective response rate (ORR) was 24.0% (3,8% complete response), disease control – 76.9%. The median PFS and OS were 6.1 and 10.6 months, respectively. As a result of treatment with ramucirumab in combination with irinotecan-based regimens, the ORR was 26.2% (4.8% complete response), disease control was 88.1%. The median PFS and OS were 7.5 and 13.3 months, respectively.

Conclusion. According to the obtained results, ramucirumab in combination with paclitaxel or the FOLFIRI regimen is an effective option for second-line therapy in DGC. The results of using ramucirumab alone or in combinations in real clinical practice in Russia are not inferior to and even numerically surpass the data from international studies and are comparable with the practical experience of other countries.

Texto integral

Acesso é fechado

Sobre autores

Natalia Besova

N.N. Blokhin National Medical Research Center of Oncology

Autor responsável pela correspondência
Email: besovans@mail.ru
ORCID ID: 0000-0002-1693-0523

Cand. Sci. (Med.), Leading Researcher, Department of Antitumor Drug Therapy No. 2, Division of Drug Treatment

Rússia, Moscow

T. Titova

N.N. Blokhin National Medical Research Center of Oncology

Email: besovans@mail.ru
ORCID ID: 0000-0002-5039-6360
Rússia, Moscow

A. Tryakin

N.N. Blokhin National Medical Research Center of Oncology

Email: besovans@mail.ru
ORCID ID: 0000-0003-0428-260X
Rússia, Moscow

E. Artamonova

N.N. Blokhin National Medical Research Center of Oncology

Email: besovans@mail.ru
ORCID ID: 0000-0002-8936-3590
Rússia, Moscow

D. Stroyakovsky

Moscow City Oncology Hospital No. 62

Email: besovans@mail.ru
Rússia, Moscow Region

E. Perminova

Moscow City Oncology Hospital No. 62

Email: besovans@mail.ru
ORCID ID: 0000-0001-5043-0859
Rússia, Moscow Region

D. Yukalchuk

Regional Oncology Dispensary

Email: besovans@mail.ru
ORCID ID: 0000-0002-0389-0980
Rússia, Irkutsk

D. Ponomarenko

Regional Oncology Dispensary

Email: besovans@mail.ru
ORCID ID: 0000-0003-0422-6755
Rússia, Irkutsk

N. Belyak

City Clinical Oncology Dispensary

Email: besovans@mail.ru
Rússia, Saint Petersburg

R. Orlova

City Clinical Oncology Dispensary

Email: besovans@mail.ru
ORCID ID: 0000-0002-9368-5517
Rússia, Saint Petersburg

G. Teletaeva

N.N. Petrov National Medical Research Center of Oncology

Email: besovans@mail.ru
Rússia, Saint Petersburg

E. Ratner

Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan

Email: besovans@mail.ru
Rússia, Kazan

A. Mochalova

MEDSI Group of Companies

Email: besovans@mail.ru
Rússia, Moscow

A. Zhabina

N.N. Petrov National Medical Research Center of Oncology

Email: besovans@mail.ru
Rússia, Saint Petersburg

S. Gamayunov

Campus of the National Medical Research Radiological Center

Email: besovans@mail.ru
ORCID ID: 0000-0001-6876-8786

Medical Radiological Research Center n.a. A.F. Tsyb 

Rússia, Obninsk

A. Smolin

N.N. Burdenko Main Military Clinical Hospital

Email: besovans@mail.ru
Rússia, Moscow

A. Povyshev

District Clinical Hospital

Email: besovans@mail.ru
ORCID ID: 0000-0002-8301-4533
Rússia, Tyumen Region, Khanty-Mansiysk

M. Andrievskikh

Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine

Email: besovans@mail.ru
ORCID ID: 0000-0001-8331-9831
Rússia, Chelyabinsk

I. Stilidi

N.N. Blokhin National Medical Research Center of Oncology

Email: besovans@mail.ru
ORCID ID: 0000-0002-0493-1166
Código SPIN: 9622-7106
Scopus Author ID: 6602949492
Rússia, Moscow

Bibliografia

  1. Vanhoefer U., Rougier P., Wilke H., 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 Co-operative Group. J Clin Oncol. 2000;18:2648–57. doi: 10.1200/JCO.2000.18.14.2648.
  2. Kang Y.K., Kang W.K., Shin D.B., et al. Capeci-tabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009;20(4):666–73. doi: 10.1093/annonc/mdn717.
  3. Al-Batran S.-E., Hartmann J.T., Probst S., et al. Phase III Trial in Metastatic Gastroesophageal Adenocarcinoma with Fluorouracil, Leucovorin Plus Either Oxaliplatin or Cisplatin: A Study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008;26:1435–42. doi: 10.1200/JCO.2007.13.9378.
  4. 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):959–63. doi: 10.1038/sj.bjc.6603046.
  5. Zaanan A., Bouche O., de la Fouchardiere C., et al. 5-fluorouracil and oxaliplatin with or without docetaxel in the first-line treatment of HER2 negative locally advanced (LA) unresectable or metastatic gastric or gastro-esophageal junction (GEJ) adenocarcinoma (GASTFOX-PRODIGE 51): A randomized phase III trial sponsored by the FFCD. Ann Oncol. 2023;34(4):s1318 (A LBA77). doi: 10.1016/j.annonc.2023.10.078.
  6. Ramaswamy A., Bhargava P.G., Biswajit D., et al. A two-arm randomized open-label prospective design superiority phase III clinical trial to compare the efficacy of docetaxel-oxaliplatin-capecitabine/5 fluorouracil (DOC/F) followed by docetaxel versus CAPOX/mFOLFOX-7 in advanced gastric cancers (DOC-GC study). J. Clin. Oncol. 2024;42(Suppl. 3). doi: 10.1200/JCO.2024.42.3 suppl.LBA248.
  7. 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 gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97. doi: 10.1016/S0140-6736(10)61121-X.
  8. Janjigian Y.Y., Shitara K., Moehler M.H., et al. Nivolumab (NIVO) plus Chemotherapy (Chemo) vs. Chemo as First-Line (1L) Treatment for Advanced Gastric Cancer/Gastroesophageal Junction Cancer/Esophageal Adenocarcinoma (GC/GEJC/EAC): 3-Year Follow-up from CheckMate 649. J Clin Oncol. 2023;41:291. doi: 10.1200/JCO.2023.41.4_suppl.291.
  9. Rha S.Y., Wyrwicz L.S., Weber P.E.Y., et al. VP1-2023: Pembrolizumab (pembro) plus chemotherapy (chemo) as first-line therapy for advanced HER2-negative gastric or gastroesophageal junction (G/GEJ) cancer: Phase III KEYNOTE-859 study. Ann Onc. 2023;34(3):319–20. doi: 10.1016/j.annonc.2023.01.006
  10. Rha S.Y., Kawazoe A., Bai Y., et al. 130O The phase III, randomized, double-blind, placebo-controlled KEYNOTE-811 study of pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Ann Oncol. 2023;34(4):1521–22. doi: 10.1016/j.annonc.2023.10.266.
  11. Thuss-Patience P.C., Kretzschmar A., Bichev D., 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):2306–14. doi: 10.1016/j.ejca.2011.06.002.
  12. Ford H.E., Marshall A., Bridgewater J.A., et al. COUGAR-02 Investigators. 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.
  13. Kang J.H., Lee S.I., Lim D.H., 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):1513–18. doi: 10.1200/JCO.2011.39.4585. [Epub 2012 Mar 12]. Erratum in: J Clin Oncol. 2012;30(24):3035.
  14. Roy A.C., Park S.R., Cunningham D., et al. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann. Oncol. 2013;24(6):1567–73. doi: 10.1093/annonc/mdt002.
  15. Hironaka S., Ueda S., Yasui H., 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):4438–44. doi: 10.1200/JCO.2012.48.5805.
  16. Ohtsu A., Shah M.A., Van Cutsem E., et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011;29(30):3968–76. doi: 10.1200/JCO.2011.36.2236.
  17. Shen L., Li J., Xu J., et al. Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: randomized, double-blind, phase III study (AVATAR study). Gastric Cancer. 2015;18(1):168–76. doi: 10.1007/s10120-014-0351-5.
  18. Fuchs C.S., Shitara K., Di Bartolomeo M., et al. RAINFALL Study Group. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet. Oncol. 2019;20(3):420–35. doi: 10.1016/S1470-2045(18)30791-5. [Epub 2019 Feb 1]. Erratum in: Lancet. Oncol. 2019;20(5):e242. doi: 10.1016/S1470-2045(19)30244-X.
  19. Fuchs C.S., Tomasek J., Yong C.J., et al. REGARD Trial Investigators. 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):31–9. doi: 10.1016/S0140-6736(13)61719-5.
  20. Wilke H., Muro K., Van Cutsem E., et al. RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet. Oncol. 2014;15(11):1224–35. doi: 10.1016/S1470-2045(14)70420-6.
  21. Di Bartolomeo M., Niger M., Tirino G., et al. Ramucirumab as Second-Line Therapy in Metastatic Gastric Cancer: Real-World Data from the RAMoss Study. Targ Oncol. 2018;13:227–34. doi: 10.1007/s11523-018-0562-5.
  22. Longo F., Jorge M., Yaya R., et al. Real-life use of ramucirumab in gastric cancer in Spain: the RAMIS study. Future Oncol. 2021;17(14):1777–91. doi: 10.2217/fon-2020-1216.
  23. Valcarcel S., Gallego J., Jimenez-Fonseca P., et al. Does HER2 status influence in the benefit of ramucirumab and paclitaxel as second line treatment of advanced gastro-esophageal adenocarcinoma? Data from the AGAMENON-SEOM registry. J Cancer Res Clin Oncol. 2023;149(7):4077–89. doi: 10.1007/s00432-022-04294-6.
  24. Paulson A.S., Hess L.M., Liepa A.M., et al. Ramucirumab for the treatment of patients with gastric or gastroesophageal junction cancer in community oncology practices. Gastric Cancer. 2018;21(5):831–44. doi: 10.1007/s10120-018-0796-z.
  25. Han H.S., Kim B.J., Jee H.J., et al. Ramucirumab plus paclitaxel as second-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma: a nationwide real-world outcomes in Korea study (KCSG-ST19-16). Ther Adv Med Oncol. 2021;13:17588359211042812. doi: 10.1177/17588359211042812.
  26. Klempner S.J., Maron S.B., Chase K., et al. Initial Report of Second-Line FOLFIRI in Combination with Ramucirumab in Advanced Gastroesophageal Adenocarcinomas: A Multi-Institutional Retrospective Analysis. Oncologist. 2019;24:475–82.
  27. Бесова Н.С., Титова Т.А., Артамонова Е.В. и др. Переносимость рамуцирумаба во второй линии лечения больных диссеминированным раком желудка в рутинной клинической практике России. Медицинский совет. 2019;(19):104–13. [Besova N.S., Titova T.A., Artamonova E.V., et al. Tolerability of ramucirumab in the second-line treatment of patients with disseminated gastric cancer in routine clinical practice in Russia. Meditsinskiy sovet=Medical Council. 2019;(19):104–13. (In Russ.)]. doi: 10.21518/2079-701X-2019-19-104-113.
  28. Therasse P., Arbuck S.G., Eisenhauer E.A., 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. doi: 10.1093/jnci/92.3.205.
  29. Tomita Y., Moldovan M., Chang Lee R., et al. Salvage systemic therapy for advanced gastric and oesophago-gastric junction adenocarcinoma. Cochrane Database Syst Rev. 2020;11(11):CD012078. doi: 10.1002/14651858.CD012078.pub2.
  30. Assersohn L., Brown G., Cunningham D., et al. Phase II study of irinotecan and 5-fluorouracil/leucovorin in patients with primary refractory or relapsed advanced oesophageal and gastric carcinoma. Ann Oncol. 2004;15:64–9. doi: 10.1093/annonc/mdh007.
  31. Kim S.T., Kang W.K., Kang J.H., et al. Salvage chemotherapy with irinotecan, 5-fluorouracil and leucovorin for taxane- and cisplatin-refractory, metastatic gastric cancer. Br J Cancer 2005;92:1850–54. doi: 10.1038/sj.bjc.6602575.
  32. Sym S.J., Ryu M.H., Lee J.L., et al. Salvage chemotherapy with biweekly irinotecan, plus 5-fluorouracil and leucovorin in patients with advanced gastric cancer previously treated with fluoropyrimidine, platinum, and taxane. Am J Clin Oncol. 2008;31(2):151–56. doi: 10.1097/COC.0b013e31815878a2.
  33. Maugeri-Saccа M., Pizzuti L., Sergi D., et al. FOLFIRI as a second-line therapy in patients with docetaxel-pretreated gastric cancer: a historical cohort. J Exp Clin Cancer Res. 2013;32(1):67. doi: 10.1186/1756-9966-32-67.
  34. Ramaswamy A., Ostwal V., Gupta K., et al. Modified 5-fluorouracil/leucovorin/irinotecan as a feasible and efficacious second-line chemotherapeutic regimen in advanced gastric cancers. South Asian J Cancer. 2018;7(4):219–22. doi: 10.4103/sajc.sajc_232_17.
  35. Vogl U.M., Vormittag L., Winkler T., et al. Ramucirumab Plus Paclitaxel or FOLFIRI in Platinum-Refractory Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma-Experience at Two Centres. J Gastrointest Oncol. 2020;11(2):366–75. doi: 10.21037/jgo.2020.03.10.
  36. Бесова Н.С., Титова Т.А., Строяковский Д.Л. и др. Результаты применения рамуцирумаба с иринотеканом и фторпиримидинами во второй линии лечения больных диссеминированным раком желудка. Медицинский совет. 2019;(10):100–9. [Besova N.S., Titova T.A., Stroyakovsky D.L., et al. Results of using ramucirumab with irinotecan and fluoropyrimidines in the second-line treatment of patients with disseminated gastric cancer. Meditsinskiy sovet=Medical Council. 2019;(10):100–9. (In Russ.)]. doi: 10.21518/2079-701X-2019-10-100-109.
  37. Бесова Н.С., Титова Т.А., Трякин А.А. и др. Рамуцирумаб в комбинации с паклитакселом или FOLFIRI во второй линии лечения больных диссеминированным раком желудка после доцетаксела в первой линии в рутинной клинической практике. Медицинский совет. 2021;(Suppl. 4):64–78. [Besova N.S., Titova T.A., Tryakin A.A. et al. Ramucirumab in combination with paclitaxel or FOLFIRI in the second-line treatment of patients with disseminated gastric cancer after docetaxel in the first line in routine clinical practice. Meditsinskiy sovet=Medical Council. 2021;(Suppl. 4):64–78. (In Russ.)]. doi: 10.21518/2079-701X-2021-4S-64-78.
  38. Lorenzen S., Schwarz A., Pauligk C., et al. Ramucirumab plus irinotecan/leucovorin/5-FU versus ramucirumab plus paclitaxel in patients with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction, who failed one prior line of palliative chemotherapy: the phase II/III RAMIRIS study (AIO-STO-0415). BMC. Cancer. 2023;23:561. doi: 10.1186/s12885-023-11004-z.

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar
2. Fig. 1. Progression-free survival: red curve - ramucirumab in monotherapy, blue curve - ramucirumab + paclitaxel, green curve - ramucirumab + FOLFlRl

Baixar (91KB)
Metadados
3. Fig. 2. Overall survival: red curve - ramucirumab in monotherapy, blue curve - ramucirumab + paclitaxel, green curve - ramucirumab + FOLFIRI

Baixar (90KB)
Metadados

Declaração de direitos autorais © Bionika Media, 2024