Bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: A meta-analysis of individual patients’ data from 3 phase III studies
Open accessAbstract
BACKGROUND: The real impact of bevacizumab maintenance as single agent in metastatic colorectal cancer (mCRC) remains unclear. SAKK-41/06 and PRODIGE-9 failed to demonstrate the non-inferiority and superiority of bevacizumab versus no maintenance, respectively, while AIO-KRK-0207 showed the non-inferiority of maintenance bevacizumab versus bevacizumab and fluoropyrimidines for time to strategy failure. METHODS: Bibliography electronic databases (PubMed, MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials) were searched for English published clinical trials prospectively randomizing mCRC patients to receive bevacizumab maintenance or not after first-line chemotherapy plus bevacizumab. Individual patients' data (IPD) were provided by investigators for all included trials. Primary end-points were progression-free survival (PFS) and overall survival (OS), both from the start of induction and maintenance. Univariate and multivariate analyses for PFS and OS were performed. RESULTS: Three phase III studies - PRODIGE-9, AIO-KRK-0207 and SAKK-41/06 - were included. Considering the different timing of randomization, IPD of patients not progressed during induction and starting maintenance phase entered the analysis. 909 patients were included, 457 (50%) received bevacizumab maintenance. Median PFS from induction start was 9.6 and 8.9 months in bevacizumab group versus no maintenance group, respectively (HR 0.78; 95%CI: 0.68-0.89; p < 0.0001). Subgroups analysis for PFS showed a significant interaction according for RAS status (p = 0.048), with a maintenance benefit limited to RAS wild-type patients. No difference in terms of OS was observed. CONCLUSIONS: Despite the statistically significant PFS improvement for bevacizumab maintenance, the absolute benefit appears limited. Subgroup analysis shows a differential effect of bevacizumab maintenance in favor of RAS wild-type patients. Considering these results, maintenance therapy with fluoropyrimidine with or without bevacizumab remains the first option. Single agent bevacizumab maintenance can be considered in selected cases, such as cumulative toxicity or patient's refusal, in particular for RAS wild-type patients.
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A meta-analysis by Lisa Salvatore et al. revealed consistent benefits with bevacizumab across clinical subgroups, except for patients with RAS mutations.
“Moreover, a meta-analysis by Lisa Salvatore et al. revealed consistent benefits with bevacizumab across clinical subgroups, except for patients with RAS mutations [40].”
From RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches (2025) · cites this paper as [40]
In exploratory analysis, greater benefit from bevacizumab as single agent was seen in RAS WT patients (HR 0.56, 95% CI 0.37-0.83) compared to RAS mutations (HR 0.91, 95% CI 0.70-1.18), with significant interaction between maintenance therapy and RAS status (p=0.048).
“Exploratory analysis showed a greater benefit from bevacizumab as a single agent in RAS WT patients (HR 0.56, 95% CI: 0.37–0.83) compared to patients with RAS mutations (HR 0.91, 95% CI: 0.70–1.18), indicating a significant interaction between maintenance therapy and RAS status (p = 0.048).”
From RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches (2025) · cites this paper as [40]
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Sütcüoğlu, O., Yıldırım, H. Ç., Almuradova, E., Günenç, D., & Yalçın, Ş. (2025) · Medicina · doi:10.3390/medicina61071202 · Cited by 10 · see citing works
- Authors
- Salvatore, L., Bria, E., Sperduti, I., Hinke, A., Hegewisch-Becker, S., Aparicio, T., Le Malicot, K., Boige, V., Koeberle, D., Baertschi, D., Dietrich, D., Tortora, G., & Arnold, D.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- Instituto Nazionale Tumori Regina Elena (IT)
- Université Paris Cité (FR)
- Institut Gustave Roussy (FR)
- University of Bern (CH)
- Swiss Group For Clinical Cancer Research (CH)
- Asklepios Klinik Altona (DE)
- Corresponding author
- Salvatore, Lisa
- ORCID
- Venue
- Cancer Treatment Reviews
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 97
- Pages
- 102202
- ISSN
- 0305-7372 (ISSN-L)
- OpenAlex
- W3150599205
- Cited by
- 26
- References
- 17
- Citations by year
- 2025: 8 · 2024: 4 · 2023: 7 · 2022: 7
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cancer Treatment Reviews (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, cc-by-nc-nd)
- Funders
- Associazione Italiana per la Ricerca sul Cancro (IG20583, 5x1000 21052, IG18599)
- Università Cattolica del Sacro Cuore (D1-2019/2020)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Surgery › Intraperitoneal and Appendiceal Malignancies
- Keywords
- bevacizumab, maintenance therapy, metastatic colorectal cancer, progression-free survival, overall survival, RAS wild-type, fluoropyrimidine, first-line chemotherapy, subgroup analysis, anti-VEGF therapy
- MeSH terms
- Bevacizumab, Antineoplastic Agents, Immunological, Humans, Prognosis, Colorectal Neoplasms, Clinical Trials, Phase III as Topic, Maintenance Chemotherapy
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