Bevacizumab Maintenance Versus No Maintenance During Chemotherapy-Free Intervals in Metastatic Colorectal Cancer: A Randomized Phase III Trial (PRODIGE 9)
Open accessAbstract
Purpose: Conflicting results are reported for maintenance treatment with bevacizumab during chemotherapy-free intervals (CFI) in metastatic colorectal cancer after induction chemotherapy. Patients and Methods: In this open-label, phase III, randomized controlled trial, we compared the tumor control duration (TCD) observed with bevacizumab maintenance and with no treatment (observation) during CFI subsequent to induction chemotherapy with 12 cycles of fluorouracil, leucovorin, and irinotecan plus bevacizumab. After disease progression, the induction regimen was repeated for eight cycles, followed by a new CFI. Results: From March 2010 to July 2013, 491 patients were randomly assigned. Disease progression or death occurred during induction chemotherapy in 85 patients (17%); 261 patients (53%) had at least one reinduction, 107 (22%) had two reinductions, and 56 (11%) had three or more reinductions. The median TCD was 15 months in both groups; the median progression-free survival (PFS) from randomization was 9.2 and 8.9 months in the maintenance group and observation groups, respectively. The TCD observed in both groups was higher compared with the TCD hypotheses of the trial. The median overall survival (OS) was 21.7 and 22.0 months in the maintenance and observation groups, respectively. In the per-protocol population, defined as patients with at least one reinduction after the first progression, the median duration of the first CFI was 4.3 months in both arms; the median TCD was 17.8 and 23.3 months ( P = .339), the median PFS was 9.9 and 9.5 months, and the median OS was 27.6 and 28.5 months in the maintenance and observation groups, respectively. Multivariable analysis revealed that female gender, WHO performance status ≥ 2, and unresected primary tumors were associated with a shorter TCD. Conclusion: Bevacizumab maintenance monotherapy did not improve TCD, CFI duration, PFS, or OS.
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Bevacizumab maintenance therapy during chemotherapy-free intervals demonstrated no benefit in overall survival or progression-free survival.
“This trial demonstrated no benefit in overall survival or progression-free survival for bevacizumab maintenance therapy.”
From Update on Targeted Therapy and Immunotherapy for Metastatic Colorectal Cancer (2024) · cites this paper as [50]
In PRODIGE-9, subgroup assessment for mPFS indicated favorable HR of bevacizumab as single agent in KRAS WT patients versus no maintenance (0.72, 95% CI 0.54-0.95), but not significant in KRAS mutation patients (HR 1.07, 95% CI 0.79-1.44).
“In the PRODIGE-9 study, subgroup assessment for mPFS indicated a favorable HR of bevacizumab as a single agent in KRAS WT patients compared to those receiving no maintenance: 0.72 (95% CI 0.54–0.95), but this was not significant in KRAS mutation patients (HR: 1.07, 95% CI 0.79–1.44) [39].”
From RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches (2025) · cites this paper as [39]
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References 20 · Cited by 91
- Authors
- Aparicio, T., Ghiringhelli, F., Boige, V., Le Malicot, K., Taieb, J., Bouché, O., Phelip, J.-M., François, E., Borel, C., Faroux, R., Dahan, L., Jacquot, S., Genet, D., Khemissa, F., Suc, E., Desseigne, F., Texereau, P., Lepage, C., Bennouna, J., & PRODIGE 9 Investigators
- Affiliations
- Inserm (FR)
- Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy,...
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2018-03-01
- Volume
- 36
- Issue
- 7
- Pages
- 674-681
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2784207302
- Cited by
- 91
- References
- 20
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 6 · 2023: 12 · 2022: 4 · 2021: 18 · 2020: 16 · 2019: 12 · 2018: 13
- FWCI
- 5.58
- Type
- journal article
- Language
- en
- Open access
- green
- ube.hal.science
- Licence
- other-oa
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- 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, chemotherapy-free interval, progression-free survival, overall survival, FOLFOXIRI, reinduction chemotherapy, prognostic factors
- MeSH terms
- Bevacizumab, Antineoplastic Agents, Immunological, Aged, Female, Humans, Male, Middle Aged, Neoplasm Metastasis, Time Factors, Colorectal Neoplasms, Disease-Free Survival, Induction Chemotherapy
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