open access

Vol 17, No 1 (2021)
Review paper
Published online: 2020-09-29
Get Citation

Bevacizumab or standard chemotherapy in previously treated patients with metastatic colorectal cancer — a systematic review

Marcin Kaczor, Wojciech Staśkiewicz, Monika Homa, Magdalena Górecka, Rafał Wójcik, Piotr Potemski
DOI: 10.5603/OCP.2020.0011
·
Oncol Clin Pract 2021;17(1):14-27.

open access

Vol 17, No 1 (2021)
REVIEW ARTICLES
Published online: 2020-09-29

Abstract

Introduction. The BRAF V600E mutation (BRAFmt) occurring in the metastatic colorectal cancer (mCRC) patients is associated with poorer prognosis, in comparison to the wild-type variant of the BRAF gene (BRAFwt). Aim of this work was to assess the clinical efficacy of bevacizumab (BEVA) or standard chemotherapy (ChT) in the 2nd or further lines of treatment in mCRC BRAFmt population. 

Material and methods. MEDLINE/PubMed, Embase and Cochrane CENTRAL databases were systematically searched. The reference lists of relevant studies were also checked. 

Results. 6 eligible trials were identified: MOMA (BEVA ± ChT), allowing for limited overall survival (OS) assessment, WJOG 6210G (BEVA + FOLFIRI), RAISE and 20050181 (FOLFIRI), PICCOLO and Spindler 2013 (irinotecan monotherapy). None of those trials were designed for the treatment evaluation in BRAFmt population. Available evidence was restricted to limited analyses in small subgroups (from a few to several dozens of patients), occasionally comprising RAS gene mutation (RASmt) as well. Based on the identified studies, the comparison of BEVA ± ChT vs. ChT or among different ChTs in BRAFmt population was not feasible. In case of BEVA (MOMA), OS hazard ratio (HR) for BRAFmt vs. BRAFwt was 1.52 (95% CI: 0.79–2.89) with difference in medians equal to 12.1 months (19.2 vs. 31.3 months, respectivelly), and BRAFmt or RASmt patients had median OS lower by 7.9 months and median progression free survival (PFS) by 3.0 months in WJOG 6210G trial. In case of ChT, median PFS was lower in BRAFmt by 12–67% (HRs range: 1.01–5.3), and median OS by 34–73% (HRs range: 1.05–5.00). 

Conclusions. Due to limited clinical evidence, assessment of further lines of treatment in BRAFmt mCRC patients is uncertain, however existing data consistently suggest lower effectiveness of BEVA ± ChT or ChT in BRAFmt, than in BRAFwt subgroup. Hopefully, combining anti-EGFR therapies with BRAF/MEK inhibitor is expected to improve prognosis of those patients.

Abstract

Introduction. The BRAF V600E mutation (BRAFmt) occurring in the metastatic colorectal cancer (mCRC) patients is associated with poorer prognosis, in comparison to the wild-type variant of the BRAF gene (BRAFwt). Aim of this work was to assess the clinical efficacy of bevacizumab (BEVA) or standard chemotherapy (ChT) in the 2nd or further lines of treatment in mCRC BRAFmt population. 

Material and methods. MEDLINE/PubMed, Embase and Cochrane CENTRAL databases were systematically searched. The reference lists of relevant studies were also checked. 

Results. 6 eligible trials were identified: MOMA (BEVA ± ChT), allowing for limited overall survival (OS) assessment, WJOG 6210G (BEVA + FOLFIRI), RAISE and 20050181 (FOLFIRI), PICCOLO and Spindler 2013 (irinotecan monotherapy). None of those trials were designed for the treatment evaluation in BRAFmt population. Available evidence was restricted to limited analyses in small subgroups (from a few to several dozens of patients), occasionally comprising RAS gene mutation (RASmt) as well. Based on the identified studies, the comparison of BEVA ± ChT vs. ChT or among different ChTs in BRAFmt population was not feasible. In case of BEVA (MOMA), OS hazard ratio (HR) for BRAFmt vs. BRAFwt was 1.52 (95% CI: 0.79–2.89) with difference in medians equal to 12.1 months (19.2 vs. 31.3 months, respectivelly), and BRAFmt or RASmt patients had median OS lower by 7.9 months and median progression free survival (PFS) by 3.0 months in WJOG 6210G trial. In case of ChT, median PFS was lower in BRAFmt by 12–67% (HRs range: 1.01–5.3), and median OS by 34–73% (HRs range: 1.05–5.00). 

Conclusions. Due to limited clinical evidence, assessment of further lines of treatment in BRAFmt mCRC patients is uncertain, however existing data consistently suggest lower effectiveness of BEVA ± ChT or ChT in BRAFmt, than in BRAFwt subgroup. Hopefully, combining anti-EGFR therapies with BRAF/MEK inhibitor is expected to improve prognosis of those patients.

Get Citation

Keywords

BRAF; colorectal cancer; systematic review; bevacizumab; chemotherapy

About this article
Title

Bevacizumab or standard chemotherapy in previously treated patients with metastatic colorectal cancer — a systematic review

Journal

Oncology in Clinical Practice

Issue

Vol 17, No 1 (2021)

Article type

Review paper

Pages

14-27

Published online

2020-09-29

DOI

10.5603/OCP.2020.0011

Bibliographic record

Oncol Clin Pract 2021;17(1):14-27.

Keywords

BRAF
colorectal cancer
systematic review
bevacizumab
chemotherapy

Authors

Marcin Kaczor
Wojciech Staśkiewicz
Monika Homa
Magdalena Górecka
Rafał Wójcik
Piotr Potemski

References (39)
  1. Potocki PM, Wysocki PJ. BRAF — a new therapeutic target in colorectal cancer. Oncol Clin Pract 2018; 14, doi: 10.5603/OCP.2018.0013.
  2. Ducreux M, Chamseddine A, Laurent-Puig P, et al. Molecular targeted therapy of BRAF-mutant colorectal cancer. Ther Adv Med Oncol. 2019; 11: 1758835919856494.
  3. Zaleśna I, Hartman ML, Czyż M. [BRAF mutation in progression and therapy of melanoma, papillary thyroid carcinoma and colorectal adenocarcinoma]. Postepy Hig Med Dosw (Online). 2016; 70: 471–488.
  4. Rad R, Cadiñanos J, Rad L, et al. A genetic progression model of Braf(V600E)-induced intestinal tumorigenesis reveals targets for therapeutic intervention. Cancer Cell. 2013; 24(1): 15–29.
  5. Clancy C, Burke JP, Kalady MF, et al. BRAF mutation is associated with distinct clinicopathological characteristics in colorectal cancer: a systematic review and meta-analysis. Colorectal Dis. 2013; 15(12): e711–e718.
  6. Tran B, Kopetz S, Tie J, et al. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer. 2011; 117(20): 4623–4632.
  7. Benson AB, Venook AP, Al-Hawary MM, et al. NCCN Clinical Practice Guidelines in Oncology — Colon Cancer. Version 1.2020 — December 19, 2019.
  8. Seppälä TT, Böhm JP, Friman M, et al. Combination of microsatellite instability and BRAF mutation status for subtyping colorectal cancer. Br J Cancer. 2015; 112(12): 1966–1975.
  9. Krakowska M, Potemski P. New treatment options for patients with metastatic colorectal cancer in Poland. Oncol Clin Pract. 2017; 13: 156–160.
  10. Seligmann JF, Fisher D, Smith CG, et al. Investigating the poor outcomes of BRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials. Ann Oncol. 2017; 28(3): 562–568.
  11. Masi G, Loupakis F, Salvatore L, et al. Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Lancet Oncol. 2010; 11(9): 845–852.
  12. Loupakis F, Cremolini C, Salvatore L, et al. FOLFOXIRI plus bevacizumab as first-line treatment in BRAF mutant metastatic colorectal cancer. Eur J Cancer. 2014; 50(1): 57–63.
  13. Cremolini C, Loupakis F, Antoniotti C, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015; 16(13): 1306–1315.
  14. Obwieszczenie Ministra Zdrowia z dnia dnia 20 grudnia 2019 r. w sprawie wykazu refundowanych leków, środków spożywczych specjalnego przeznaczenia żywieniowego oraz wyrobów medycznych na 1 stycznia 2020 r.
  15. Pietrantonio F, Petrelli F, Coinu A, et al. Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: a meta-analysis. Eur J Cancer. 2015; 51(5): 587–594.
  16. Rowland A, Dias MM, Wiese MD, et al. Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer. Br J Cancer. 2015; 112(12): 1888–1894.
  17. Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019; 366: l4898.
  18. Sterne JAc, Hernán MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016; 355: i4919.
  19. Wytyczne oceny technologii medycznych (HTA, ang. health technology assessment), wersja 3.0. Agencja Oceny Technologii Medycznych i Taryfikacji, Warszawa, sierpień 2016.
  20. Cremolini C, Antoniotti C, Rossini D, et al. GONO Foundation Investigators. Phase II randomised study of maintenance treatment with bevacizumab or bevacizumab plus metronomic chemotherapy after first-line induction with FOLFOXIRI plus Bevacizumab for metastatic colorectal cancer patients: the MOMA trial. Eur J Cancer. 2019; 109: 175–182.
  21. Shitara K, Yonesaka K, Denda T, et al. Randomized study of FOLFIRI plus either panitumumab or bevacizumab for wild-type KRAS colorectal cancer-WJOG 6210G. Cancer Sci. 2016; 107(12): 1843–1850.
  22. Yoshino T, Portnoy DC, Obermannová R, et al. Biomarker analysis beyond angiogenesis: RAS/RAF mutation status, tumour sidedness, and second-line ramucirumab efficacy in patients with metastatic colorectal carcinoma from RAISE-a global phase III study. Ann Oncol. 2019; 30(1): 124–131.
  23. Peeters M, Oliner KS, Price TJ, et al. Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer. Clin Cancer Res. 2015; 21(24): 5469–5479.
  24. Seymour MT, Brown SR, Middleton G, et al. Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial. Lancet Oncol. 2013; 14(8): 749–759.
  25. Spindler KG, Appelt AL, Pallisgaard N, et al. KRAS-mutated plasma DNA as predictor of outcome from irinotecan monotherapy in metastatic colorectal cancer. Br J Cancer. 2013; 109(12): 3067–3072.
  26. Sanz-Garcia E, Argiles G, Elez E, et al. BRAF mutant colorectal cancer: prognosis, treatment, and new perspectives. Ann Oncol. 2017; 28(11): 2648–2657.
  27. Maughan TS, Adams RA, Smith CG, et al. MRC COIN Trial Investigators. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet. 2011; 377(9783): 2103–2114.
  28. Adams RA, Meade AM, Seymour MT, et al. MRC COIN Trial Investigators. Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet Oncol. 2011; 12(7): 642–653.
  29. Seymour MT, Maughan TS, Ledermann JA, et al. FOCUS Trial Investigators, National Cancer Research Institute Colorectal Clinical Studies Group. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet. 2007; 370(9582): 143–152.
  30. Prahallad A, Sun C, Huang S, et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature. 2012; 483(7387): 100–103.
  31. Corcoran RB, Ebi H, Turke AB, et al. EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib. Cancer Discov. 2012; 2(3): 227–235.
  32. Kopetz S, Grothey A, Yaeger R, et al. Encorafenib, binimetinib, and cetuximab in v600e-mutated colorectal cancer. N Engl J Med. 2019; 381(17): 1632–1643.
  33. Corcoran RB, André T, Atreya CE, et al. Combined BRAF, EGFR, and MEK inhibition in patients with -mutant colorectal cancer. Cancer Discov. 2018; 8(4): 428–443.
  34. Tabernero J, Takayuki Y, Cohn AL, et al. RAISE Study Investigators. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 2015; 16(5): 499–508.
  35. Peeters M, Price TJ, Cervantes A, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010; 28(31): 4706–4713.
  36. Ursem C, Atreya CE, Van Loon K. Emerging treatment options for -mutant colorectal cancer. Gastrointest Cancer. 2018; 8: 13–23.
  37. Kopetz S, Grothey A, Cutsem EV, et al. Encorafenib plus cetuximab with or without binimetinib for BRAF V600E-mutant metastatic colorectal cancer: Quality-of-life results from a randomized, three-arm, phase III study versus the choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC). J Clin Oncol. 2020; 38(4_suppl): 8–8.
  38. Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017; 18(9): 1182–1191.
  39. Morse MA, Hochster H, Benson Al. Perspectives on treatment of metastatic colorectal cancer with immune checkpoint inhibitor therapy. Oncologist. 2020; 25(1): 33–45.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Wydawcą serwisu jest  "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl