Overall Survival and Progression-Free Survival Comparison of Bevacizumab Plus Chemotherapy Combination Regiment Versus Chemotherapy Only Regiment in Metastatic Colorectal Cancer: A Comparative Meta-Analysis and Systematic Review
DOI:
https://doi.org/10.37287/ijghr.v8i4.1402Keywords:
bevacizumab, chemotherapy, metastatic colorectal cancer, overall survival, progression-free survivalAbstract
Bevacizumab’s role in enhancing chemotherapy’s efficacy by inhibiting tumor vasculature has led to its incorporation in both first-line and second-line treatment protocols for mCRC. This meta-analysis and systematic review aim to provide a comprehensive comparison of the overall survival (OS) and progress-free survival (PFS) of bevacizumab plus chemotherapy versus chemotherapy alone in patients with metastatic colorectal cancer. A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines using the PICO framework. Rigorous screening, data extraction, risk of bias assessment, and statistical analysis were performed to investigate the OS and PFS of bevacizumab plus chemotherapy versus chemotherapy alone in patients with metastatic colorectal cancer. A total of 79 articles were retrieved from online databases (PubMed, SagePub, Nature and Cochrane) using combinations terms such as “metastatic colorectal cancer,” “bevacizumab,” “chemotherapy,” “overall survival,” and “progression-free survival.” After three rounds of screening, seven articles directly relevant to the meta-analysis were selected for full-text reading and analysis. The pooled OS across all studies is 0.79 (95% CI: [0.68, 0.93]), indicating a statistically significant overall survival benefit for bevacizumab plus chemotherapy. The pooled PFS across studies was 0.68 (95% CI: 0.54–0.87), strongly favoring the combination therapy for improved PFS. Bevacizumab plus chemotherapy offers survival benefits for metastatic colorectal cancer, especially in overall survival. However, increased risks of hypertension and bleeding require careful patient selection and monitoring. Ongoing research is needed to optimize treatment protocols and safety.
References
Van Cutsem, E., Danielewicz, I., Saunders, M. P., et al. (2020). Trifluridine/tipiracil plus bevacizumab in patients with untreated metastatic colorectal cancer ineligible for intensive therapy: The randomized TASCO1 study. Annals of Oncology, 31(9), 1160–1168.
Aranda, E., García-Alfonso, P., Benavides, M., et al. (2018). First-line mFOLFOX plus cetuximab followed by mFOLFOX plus cetuximab or single-agent cetuximab as maintenance therapy in patients with metastatic colorectal cancer: Phase II randomised MACRO2 TTD study. European Journal of Cancer, 101, 263–272.
Loupakis, F., Cremolini, C., Masi, G., et al. (2014). Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. New England Journal of Medicine, 371(17), 1609–1618. https://doi.org/10.1056/NEJMoa1403108
Qu, C. Y., Zheng, Y., Zhou, M., et al. (2015). Value of bevacizumab in treatment of colorectal cancer: A meta-analysis. World Journal of Gastroenterology, 21(16), 5072.
Rosen, L. S., Jacobs, I. A., & Burkes, R. L. (2017). Bevacizumab in colorectal cancer: Current role in treatment and the potential of biosimilars. Targeted Oncology, 12(5), 599–610. https://doi.org/10.1007/s11523-017-0518-1
Baraniskin, A., Buchberger, B., Pox, C., et al. (2019). Efficacy of bevacizumab in first-line treatment of metastatic colorectal cancer: A systematic review and meta-analysis. European Journal of Cancer, 106, 37–44.
Prager, G. W., Taieb, J., Fakih, M., et al. (2023). Trifluridine–tipiracil and bevacizumab in refractory metastatic colorectal cancer. New England Journal of Medicine, 388(18), 1657–1667. https://doi.org/10.1056/NEJMoa2214963
Rinaldi, I., Winston, K., Vincent, L. D., et al. (2022). Overall survival and progression-free survival comparison of bevacizumab plus chemotherapy combination regiment versus chemotherapy only regiment in previously untreated metastatic colorectal cancer: Systematic review and meta-analysis. Open Access Macedonian Journal of Medical Sciences, 10(F), 269–277. https://doi.org/10.3889/oamjms.2022.9375
Venook, A. P., Niedzwiecki, D., Lenz, H. J., et al. (2017). Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer: A randomized clinical trial. JAMA, 317(23), 2392–2401.
Botrel, T. E. A., Clark, L. G. D. O., Paladini, L., & Clark, O. A. C. (2016). Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: A systematic review and meta-analysis. BMC Cancer, 16(1), 677. https://doi.org/10.1186/s12885-016-2734-y
Yamazaki, K., Nagase, M., Tamagawa, H., et al. (2016). Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G). Annals of Oncology, 27(8), 1539–1546.
Heinemann, V., von Weikersthal, L. F., Decker, T., et al. (2014). FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): A randomised, open-label, phase 3 trial. The Lancet Oncology, 15(10), 1065–1075.
Aparicio, T., Bouché, O., Taieb, J., et al. (2018). Bevacizumab plus chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: A randomized phase II trial—PRODIGE 20 study results. Annals of Oncology, 29(11), 2270. https://doi.org/10.1093/annonc/mdx808
Cunningham, D., Lang, I., Marcuello, E., et al. (2013). Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): An open-label, randomised phase 3 trial. The Lancet Oncology, 14(11), 1077–1085. https://doi.org/10.1016/S1470-2045(13)70154-2
Guan, Z. Z., Xu, J. M., Luo, R. C., et al. (2011). Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: A randomized phase III ARTIST trial. Chinese Journal of Cancer, 30(10), 682–689. https://doi.org/10.5732/cjc.011.10188
Khakoo, S., Chau, I., Pedley, I., et al. (2019). ACORN: Observational study of bevacizumab in combination with first-line chemotherapy for treatment of metastatic colorectal cancer in the UK. Clinical Colorectal Cancer, 18(4), 280–291.e5. https://doi.org/10.1016/j.clcc.2019.07.003
Passardi, A., Nanni, O., Tassinari, D., et al. (2015). Effectiveness of bevacizumab added to standard chemotherapy in metastatic colorectal cancer: Final results for first-line treatment from the ITACa randomized clinical trial. Annals of Oncology, 26(6), 1201–1207. https://doi.org/10.1093/annonc/mdv130
Tahover, E., Hubert, A., Temper, M., et al. (2015). An observational cohort study of bevacizumab and chemotherapy in metastatic colorectal cancer patients: Safety and efficacy with analysis by age group. Targeted Oncology, 10(1), 55–63. https://doi.org/10.1007/s11523-014-0311-3
Tang, W., Ren, L., Liu, T., et al. (2020). Bevacizumab plus mFOLFOX6 versus mFOLFOX6 alone as first-line treatment for RAS mutant unresectable colorectal liver-limited metastases: The BECOME randomized controlled trial. Journal of Clinical Oncology, 38(27), 3175–3184. https://doi.org/10.1200/JCO.20.00174
Gao, J., Li, F., Liu, Z., et al. (2021). Multiple genetic variants predict the progression-free survival of bevacizumab plus chemotherapy in advanced ovarian cancer: A retrospective study. Medicine, 100(35), e27130.
Luo, H. Y., Li, Y. H., Wang, W., et al. (2016). Single-agent capecitabine as maintenance therapy after induction of XELOX (or FOLFOX) in first-line treatment of metastatic colorectal cancer: Randomized clinical trial of efficacy and safety. Annals of Oncology, 27(6), 1074–1081.
Wang, J., Luo, L., Wang, D., et al. (2018). Combination adjuvant chemotherapy with targeted drugs for treatment of colorectal cancer: A network meta-analysis. Journal of Cellular Biochemistry, 119(2), 1521–1537. https://doi.org/10.1002/jcb.26312
Qu, F. J., Wu, S., & Kong, Y. (2023). Oral fruquintinib combined with tegafur-gimeracil-oteracil potassium for advanced colorectal cancer to obtain longer progression-free survival: A case report. World Journal of Gastrointestinal Oncology, 15(5), 902.
Ma, H., Wu, X., Tao, M., et al. (2019). Efficacy and safety of bevacizumab-based maintenance therapy in metastatic colorectal cancer: A meta-analysis. Medicine, 98(50), e18227.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Indonesian Journal of Global Health Research
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
