Real-World Outcomes of Irinotecan–Bevacizumab Therapy in Recurrent Brain Tumors: A Retrospective Cohort Study

By /
Cite this article Download PDF DOI Email Share
Mustafa Seyyar, Pervin Can Şancı, Ali Kalem, Burak Mete, Tolga Köşeci, Anıl Karakayalı, Mehmet Uzun, Teoman Sakalar, Yasemin Bakkal Temi, Melike Yazıcı, Devrim Çabuk, Umut Kefeli, Kazım Uygun

Volume 9 · Issue 1 · pp. 132–137

Received: 20251227  Accepted: 20260304  Published: 20260317

Abstract

Abstract Aim: Although the irinotecan–bevacizumab (IB) combination is a frequently used treatment option in recurrent brain tumors, clinical benefit shows heterogeneity among patient subgroups. This study aimed to evaluate clinical and prognostic factors associated with early-stage mortality and overall survival (OS) in patients receiving IB treatment. Material and Methods: Seventy-eight brain tumor patients who received IB treatment between 2015 and 2023 were retrospectively evaluated. Patients with complete clinical and radiological data were included in the study. The demographic, clinical, and pathological characteristics of the patients were recorded. The timing of the initiation of IB therapy was categorized according to whether it was started at the first recurrence or at the second and subsequent recurrences. Factors associated with early-stage mortality (≤6 months) were determined using log-linear regression analysis, while independent prognostic factors affecting GSK were determined using the Cox proportional hazards regression model. Results: The mean age of patients was 53.01±12.78 years, and the mean follow-up period was 9.47 months. The mortality rate within the first 6 months was determined to be 44.9%. Early-stage mortality was found to be significantly associated with multilobular tumor localization (p=0.037) and initiation of IB therapy at ≥2nd stage (p=0.036). In the log-linear regression analysis, the probability of survival beyond 6 months was 5.05 times lower (RR=0.198, 95% CI: 0.054-0.735) in multilobular localization, while in those who started IB at ≥2nd node, it was 4.40 times lower (RR=0.227, 95% CI: 0.069-0.748). In the multivariate Cox regression analysis, starting IB at ≥2nd line (HR: 2.35, 95% CI: 1.09-5.07, p=0.029), the presence of IDH mutation (HR: 1.98, 95% CI: 1.09-3.58, p=0.025), and age (HR: 1.03, 95% CI: 1.01-1.05, p=0.015) were identified as independent prognostic factors for GSK. Conclusion: This retrospective cohort study based on real-world data demonstrates that the clinical benefit of the IB combination shows significant heterogeneity across patient subgroups. Multilobar tumor location and initiation of IB therapy in the late stages of recurrence are associated with early mortality and poorer survival. Our findings emphasize that IB therapy in recurrent brain tumors should be administered in a personalized manner, considering patient selection and treatment sequence, rather than as a routine approach.

Keywords: Glioblastoma multiforme; brain tumors; bevacizumab; irinotecan; overall survival

References

  1. Lim M, Xia Y, Bettegowda C, Weller M. Current state of immunotherapy for glioblastoma. Nat Rev Clin Oncol. 2018;15(7):422-442. Crossref
  2. Weller M, Wick W, Aldape K, Brada M, Berger M, Pfister SM, et al. Glioma. Nat Rev Dis Primers. 2015;1:15017. Crossref
  3. Jain RK, di Tomaso E, Duda DG, Loeffler JS, Sorensen AG, Batchelor TT. Angiogenesis in brain tumours. Nat Rev Neurosci. 2007;8(8):610-622. Crossref
  4. Ferrara N, Hillan KJ, Gerber HP, Novotny W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov. 2004;3(5):391-400. Crossref
  5. Jakobsen JN, Hasselbalch B, Stockhausen MT, Lassen U, Poulsen HS. Irinotecan and bevacizumab in recurrent glioblastoma multiforme. Expert Opin Pharmacother. 2011;12(5):825-833. Crossref
  6. Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27(28):4733-4740. Crossref
  7. Raymond E, Faivre S, Chaney S, Woynarowski J, Cvitkovic E. Cellular and molecular pharmacology of oxaliplatin. Mol Cancer Ther. 2002;1(3):227-235.
  8. Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Dowell JM, Reardon DA, Quinn JA, et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007;13(4):1253-1259. Crossref
  9. Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, et al. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol. 2014;15(9):943-953. Crossref
  10. Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, et al. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012-2016. Neuro Oncol. 2019;21(Suppl 5):v1-v100. Crossref
  11. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-996. Crossref
  12. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997-1003. Crossref
  13. Louis DN, Perry A, Wessling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):1231-1251. Crossref
  14. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010;28(11):1963-1972. Crossref
  15. Ellingson BM, Wen PY, Cloughesy TF, Abrey LE, Chang SM, Lamborn KR, et al. Modified Criteria for Radiographic Response Assessment in Glioblastoma Clinical Trials. Neurotherapeutics. 2017;14(2):307-320. Crossref
  16. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Bevacizumab plus Radiotherapy-Temozolomide for Newly Diagnosed Glioblastoma. N Engl J Med. 2014;370(8):709-722. Crossref
  17. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, et al. A Randomized Trial of Bevacizumab for Newly Diagnosed Glioblastoma. N Engl J Med. 2014;370(8):699-708. Crossref
  18. Weller M, van den Bent M, Preusser M, Le Rhun E, Tonn JC, Minniti G, et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol. 2021;18(3):170-186. Crossref
  19. Lombardi G, De Salvo GL, Brandes AA, Eoli M, Rudà R, Faedi M, et al. Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2019;20(1):110-119. Crossref
  20. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360(8):765-773. Crossref

Cite this article

Mustafa Seyyar, Pervin Can Şancı, Ali Kalem, Burak Mete, Tolga Köşeci, Anıl Karakayalı, Mehmet Uzun, Teoman Sakalar, Yasemin Bakkal Temi, Melike Yazıcı, Devrim Çabuk, Umut Kefeli, Kazım Uygun. Real-World Outcomes of Irinotecan–Bevacizumab Therapy in Recurrent Brain Tumors: A Retrospective Cohort Study. Journal of Cukurova Anesthesia and Surgical Sciences. 9(1):132-137. https://doi.org/10.36516/jocass.1849486

Scroll to Top