Preview

Surgery and Oncology

Advanced search

Efficacy and toxicity of aflibercept and bevacizumab in combination with FOLFIRI in second‑line therapy for metastatic colon cancer: a retrospective multicenter study

https://doi.org/10.17650/2686-9594-2021-11-3-4-11-17

Abstract

Objective: to compare the efficacy and toxicity of aflibercept and bevacizumab in combination with fOLfIRI in secondline therapy for patients with metastatic colon cancer.
Materials and methods. we performed a retrospective analysis of data on patients with metastatic colon cancer treated in 9 clinics in the Russian federation. The inclusion criteria were as follows: metastatic or locally advanced colon cancer; treatment with bevacizumab or aflibercept plus fOLfIRI in the second-line therapy. The primary outcome measure was progression-free survival (PfS). Secondary outcome measures included objective response rate and incidence of adverse events.
Results. A total of 271 patients with metastatic colon cancer who received second-line therapy with bevacizumab (n = 81) or aflibercept (n = 190) between 2014 and 2018 were selected for this study. Study groups were matched for main prognostic signs. The objective response rate was 18.1 % in the bevacizumab group and 20.5 % in the aflibercept group (p = 0.7). The median PfS was 5 months (95 % confidence interval 3.8–6.1) in the aflibercept group and 7 months (95 % confidence interval 0.81–2.1) in the bevacizumab group (hazard ratio 1.4; 95 % confidence interval 0.99–2.1; p = 0.04). multivariate regression analysis demonstrated that the type of the targeted drug independently had no effect on PfS (hazard ratio 1.3; 95 % confidence interval 0.9–1.9; p = 0.2). we observed no statistically significant differences in the incidence of complications of any grades between the groups (58 % vs 72 %, p = 0.1). Patients receiving aflibercept were more likely to develop grade III–Iv arterial hypertension (2 % vs 9.5 %) and diarrhea (0 % vs 5.4 %), whereas thrombotic complications were more common in the bevacizumab group (10 % vs 1.8 %).
Conclusion. we observed no significant differences in objective response rate and PfS between patients with metastatic colon cancer receiving bevacizumab or aflibercept in combination with fOLfIRI as second-line therapy. The toxicity profiles were different. Our findings can be used for choosing an optimal targeted drug for second-line treatment.

About the Authors

M.   Yu. Fedyanin
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

Mikhail Yuryevich Fedyanin 

24 Kashirskoe Shosse, Moscow 115478



L.  Yu.  Vladimirova
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

63/2 14-ya Liniya, Rostov-on-Don 344019



V.  A.  Chubenko
Saint Petersburg Clinical Research Center for Specialized Medical Care (Oncology), Ministry of Health of Russia
Russian Federation

68A Leningradskaya St., Pesochnyy, Saint Petersburg 197758



L.   A. Zagorskaya
Saint Petersburg Clinical Research Center for Specialized Medical Care (Oncology), Ministry of Health of Russia
Russian Federation

68A Leningradskaya St., Pesochnyy, Saint Petersburg 197758



A.  V.  Belyaeva
Saint Petersburg Clinical Research Center for Specialized Medical Care (Oncology), Ministry of Health of Russia
Russian Federation

68A Leningradskaya St., Pesochnyy, Saint Petersburg 197758



O.  L.  Fakhrutdinova
Saint Petersburg Clinical Research Center for Specialized Medical Care (Oncology), Ministry of Health of Russia
Russian Federation

68A Leningradskaya St., Pesochnyy, Saint Petersburg 197758



S.  A.  Belukhin
Saint Petersburg Clinical Research Center for Specialized Medical Care (Oncology), Ministry of Health of Russia
Russian Federation

68A Leningradskaya St., Pesochnyy, Saint Petersburg 197758



A.   S. Zhabina
Saint Petersburg Clinical Research Center for Specialized Medical Care (Oncology), Ministry of Health of Russia
Russian Federation

68A Leningradskaya St., Pesochnyy, Saint Petersburg 197758



L.   V. Khalikova
Saint Petersburg Clinical Research Center for Specialized Medical Care (Oncology), Ministry of Health of Russia
Russian Federation

68A Leningradskaya St., Pesochnyy, Saint Petersburg 197758



L.  V.  Bolotina
P. A. Herzen Moscow Oncology Research Institute – a branch of the National Medical Radiology Research Center, Ministry of Health of Russia
Russian Federation

3 2-oy Botkinskiy Proezd, Moscow 125284



R.   V. Orlova
Saint Petersburg State University
Russian Federation

7/9 Universitetskaya Naberezhnaya, Saint Petersburg 199034



F.  V.  Moiseenko
Saint Petersburg Clinical Research Center for Specialized Medical Care (Oncology), Ministry of Health of Russia; Saint Petersburg State University
Russian Federation

68A Leningradskaya St., Pesochnyy, Saint Petersburg 197758

7/9 Universitetskaya Naberezhnaya, Saint Petersburg 199034



G.   Z. Mukhametshina
Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Tatarstan
Russian Federation

29 Sibirskiy Trakt, Kazan 420029, Republic of Tatarstan



A.  I.  Khasanova
Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Tatarstan
Russian Federation

29 Sibirskiy Trakt, Kazan 420029, Republic of Tatarstan



A.  V.  Belonogov
Medsi Group of Companies, Clinical Hospital No. 1 «Medsi»
Russian Federation

2/1A Pyatnitskoe shosse 6 km, Otradnoye, Moscow region 143442



Kh.  S.  Musaeva
Republican Oncology Dispensary
Russian Federation

81 Leonova St., Grozny 366007, Chechen Republic



O.  Yu.  Novikova
Regional Clinical Oncology Center
Russian Federation

164 Voronezhskaya St., Khabarovsk 680035



 I.  Yu.  Stradaeva
Moscow Regional Oncology Dispensary
Russian Federation

6 Karbysheva St., Balashikha 143900



I.  L.  Popova
Saint Petersburg Clinical Oncology Dispensary
Russian Federation

56 Prospekt Veteranov, Saint Petersburg 198255



S.  P.  Erdniev
Saint Petersburg Clinical Oncology Dispensary
Russian Federation

56 Prospekt Veteranov, Saint Petersburg 198255



A.  K.  Ivanova
Saint Petersburg Clinical Oncology Dispensary
Russian Federation

56 Prospekt Veteranov, Saint Petersburg 198255



A.  V.  Androsova
Saint Petersburg Clinical Oncology Dispensary
Russian Federation

56 Prospekt Veteranov, Saint Petersburg 198255



P.  S.  Feoktistova
Nizhnevartovsk Oncology Dispensary
Russian Federation

9a Sportivnaya St., Nizhnevartovsk 628615



E.  S.  Kuzmina
Salekhard Regional Clinical Hospital
Russian Federation

39 Mira St., Salekhard 629001



E.   V. Karabina
Tula Regional Oncology Dispensary
Russian Federation

201A Plekhanova St., Tula 300040



O.  V.  Nekrasova
Multicare Medical Center “Medical City”
Russian Federation

32 Barnaulskaya St., Tyumen 625041



O.  V.  Sekhina
Oncology Dispensary No. 5, Moscow Healthcare Department
Russian Federation

5/1 Perervinskiy Bulvar, Moscow 109451



A.   A. Mishchenko
Primorsky Regional Oncology Dispensary
Russian Federation

57A Russkaya St., Vladivostok 690069



L.  A.  Mukova
Oncology Dispensary, Ministry of Health of Kabardino-Balkar Republic
Russian Federation

23 Lermontova St., Nalchik 360000, Kabardino-Balkar Republic



B.  Kh.  Kertiev
Oncology Dispensary, Ministry of Health of Kabardino-Balkar Republic
Russian Federation

23 Lermontova St., Nalchik 360000, Kabardino-Balkar Republic



G.  I.  Kosar
Oncology Dispensary
Russian Federation

46/45 Pervomayskiy Per., Volgodonsk 347360



S.   N. Osodoeva
Buryat Republican Oncology Dispensary
Russian Federation

32 Pirogova St., Ulan-Ude 670047



A.  I.  Kats
Oncology Dispensary
Russian Federation

23 Sholom-Aleykhema St., Birobidzhan 679016



R.  R.  Malina
Oncology Dispensary
Russian Federation

23 Sholom-Aleykhema St., Birobidzhan 679016



M.  A.  Lyadova
City Clinical Oncology Hospital No. 1 Moscow Healthcare Department
Russian Federation

18A Zagorodnoe Shosse, Moscow 117152



A.  A.  Tryakin
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115478



S.  A.  Tyulandin
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115478



References

1. Shinozaki E., Makiyama A., Kagawa Y. et al. Treatment sequences of patients with advanced colorectal cancer and use of second-line FOLFIRI with antiangiogenic drugs in Japan: A retrospective observational study using an administrative database. PLoS One 2021;16(2):e0246160. DOI: 10.1371/journal.pone.0246160.

2. Tournigand C., André T., Achille E. et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004;22(2):229–37. DOI: 10.1200/JCO.2004.05.113.

3. Guo W. Zhang X. Wang Y.et al. FOLFIRI versus irinotecan monodrug as second-line treatment in metastatic colorectal cancer patients: An open, multicenter, prospective, randomized controlled phase III clinical study. J Clin Oncol 2020;38(Suppl):abstr. 4038.

4. Федянин М.Ю., Гладков О.А., Гордеев С.С. и др. Практические рекомендации по лекарственному лечению рака ободочной кишки и ректосигмоидного соединения. Злокачественные опухоли: Практические рекомендации RUSSCO № 3s2, 2020 (том 10). [Fedyanin M.Yu., Gladkov O.A., Gordeev S.S. et al. Practical recommendations for pharmacotherapy of colon and rectosigmoid cancer. Malignant tumors: practical recommendations of the RUSSCO No. 3s2, 2020 (Vol. 10). (In Russ.)].

5. Федянин М.Ю., Тюляндин С.А. Выбор последовательности комбинаций химиопрепаратов и моноклональных антител в лечении больных метастатическим раком толстой кишки. Злокачественные опухоли 2018;8(2):50–9. [Fedyanin M.Yu., Tyulyandin S.A. Choosing an optimal sequence of chemotherapeutic agents and monoclonal antibodies in the treatment of patients with metastatic colon cancer. Zlokachestvennye opukholi = Malignant Tumors 2018;8(2):50–9. (In Russ.)]. DOI: 10.18027/2224-5057-2018-8-2-50-59.

6. Qiu T., Chen W., Li P. et al. Subsequent anti-VEGF therapy after first-line antiEGFR therapy improved overall survival of patients with metastatic colorectal cancer. Onco Targets Ther 2018;11:465–71. DOI: 10.2147/OTT.S149110.

7. Бесова Н.С., Титова Т.А., Артамонова Е.В. и др. Анализ факторов прогноза выживаемости российской популяции больных диссеминированным раком желудка, получивших рамуцирумаб во второй линии лечения в исследовании RAMSELGA. Медицинский cовет 2020;(9):165–74. [Besova N.S., Titova T.A., Artamonova E.V. et al. Analysis of prognostic factors affecting survival of Russian patients with disseminated gastric cancer receiving ramucirumab as second-line therapy in the RAMSELGA study. Meditsinskiy sovet = Medical Council 2020; (9):165–74. (In Russ.)]. DOI: 10.21518/2079-701X-2020-9-165-174.

8. Tryakin A., Perminova E., Stroyakovsky D. et al. Ramucirumab in the treatment of refractory metastatic gastric cancer: Results from the RamSelGa trial. Ann Oncol 2019;30(Suppl 5):v306, v307.

9. Van Cutsem E., Tabernero J., Lakomy R. et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 2012;30(28):3499–506.

10. Beretta G.D., Petrelli F., Stinco S. et al. FOLFIRI + bevacizumab as second-line therapy for metastatic colorectal cancer pretreated with oxaliplatin: a pooled analysis of published trials. Med Oncol 2013;30(1): 486. DOI: 10.1007/s12032-013-0486-y.

11. Федянин М.Ю., Моисеенко Ф.В., Лядова М.А. и др. Независимое наблюдательное исследование по оценке токсичности и эффективности биоаналога бевацизумаба во 2-й линии лечения метастатического рака толстой кишки в рутинной клинической практике. Тазовая хирургия и онкология 2021;11(1):11–20. [Fedyanin M.Yu., Moiseenko F.V., Lyadova M.A. et al. Toxicity and efficacy of biosimilar bevacizumab in the second-line therapy for metastatic colon cancer in routine clinical practice: results of an independent observational study. Tazovaya khirurgiya i onkologiya = Pelvic Surgery and Oncology 2021;11(1):11–20. (In Russ.)]. DOI: 10.17650/2686-9594-2021-11-1-11-20.

12. Орлов С.В., Фогт С.Н., Шустова М.С. Успешная регистрация отечественного биоаналога бевацизумаба – новые возможности эффективной терапии больных неплоскоклеточным немелкоклеточным раком легкого. Исследования и практика в медицине 2015;2(4):132– 36. [Orlov S.V., Fogt S.N., Shustova M.S. Successful approval of biosimilar bevacizumab produced in the Russian Federation: new opportunities for effective therapy in patients with non-squamous non-small cell lung cancer. Issledovaniya i praktika v meditsine = Research and Practice in Medicine 2015;2(4):132–36. (In Russ.)].

13. Bennouna J., Sastre J., Arnold D. et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): А randomised phase 3 trial. Lancet Oncol 2013;14(1):29–37.

14. Torregrosa C., Pernot S., Perret A. et al. Bevacizumab (bev) continuation with FOLFIRI or switch to aflibercept (afli) with FOLFIRI as second-line treatment (L2) after first line of FOLFOX-bev (L1) for metastatic colorectal cancer (mCRC): An AGEO multicenter study. Ann Oncol 2020;31(Suppl 4):S426.

15. Yamazak K., Yuki S., Ok E. et al. Realworld evidence on second-line treatment of metastatic colorectal cancer using fluoropyrimidine, irinotecan, and angiogenesis inhibitor. Clin Colorectal Cancer 2021;20(3):e173–e184. DOI: 10.1016/j.clcc.2021.03.001.

16. Ottaiano A., Capozzi M., Tafuto S. et al. Folfiri–aflibercept vs. folfiri–bevacizumab as second line treatment of RAS mutated metastatic colorectal cancer in real practice. Front Oncol 2019;9:766.


Review

Views: 516


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2949-5857 (Online)