Bevacizumab as adjuvant treatment of colon cancer: updated results from the S-AVANT phase III study by the GERCOR Group
Journal
Annals of Oncology
Journal Volume
31
Journal Issue
2
Pages
246-256
Date Issued
2020
Author(s)
Andr? T.
Vernerey D.
Im S.A.
Bodoky G.
Buzzoni R.
Reingold S.
Rivera F.
McKendrick J.
Scheithauer W.
Ravit G.
Fountzilas G.
Yong W.P.
Isaacs R.
?sterlund P.
Creemers G.J.
Rakez M.
Van Cutsem E.
Cunningham D.
Tabernero J.
de Gramont A.
Abstract
Background: The bevacizumab-Avastin? adjuVANT (AVANT) study did not meet its primary end point of improving disease-free survival (DFS) with the addition of bevacizumab to oxaliplatin-based chemotherapy in stage III colon cancer (CC). We report here the long-term survival results (S-AVANT). Patients and methods: Patients with curatively resected stage III CC were randomly assigned to FOLFOX4, FOLFOX4-bevacizumab, or XELOX-bevacizumab. Results: A total of 2867 patients were randomized: FOLFOX4: n = 955, FOLFOX4-bevacizumab: n = 960, XELOX-bevacizumab: n = 952. With a median of 6.73 years follow-up (interquartile range 5.51–10.54), 672 patients died, of whom 198 (20.7%), 250 (26.0%), and 224 (23.5%) were in the FOLFOX4, FOLFOX4-bevacizumab, and XELOX-bevacizumab arms, respectively. The 10-year overall survival (OS) rates were 74.6%, 67.2%, and 69.9%, (P = 0.003) and 5-year disease-free survival (DFS) rates were 73.2%, 68.5%, and 71.0% (P = 0.174), respectively. OS and DFS hazard ratios were 1.29 [95% confidence interval (CI) 1.07–1.55; P = 0.008] and 1.16 (95% CI 0.99–1.37; P = 0.063) for FOLFOX4-bevacizumab versus FOLFOX4 and 1.15 (95% CI 0.95–1.39; P = 0.147) and 1.1 (95% CI 0.93–1.29; P = 0.269) for XELOX-bevacizumab versus FOLFOX4, respectively. CC-related deaths (n = 542) occurred in 157 (79.3%) patients receiving FOLFOX4, 205 (82.0%) receiving FOLFOX4-bevacizumab, and 180 (80.4%) receiving XELOX-bevacizumab (P = 0.764), while non-CC-related deaths occurred in 41 (20.7%), 45 (18.0%), and 44 (19.6%) patients, respectively. Cardiovascular-related and sudden deaths during treatment or follow-up were reported in 13 (6.6%), 17 (6.8%), and 14 (6.3%) patients, in the FOLFOX4, FOLFOX4-bevacizuamb, and XELOX-bevacizumab arms, respectively (P = 0.789). Treatment arm, sex, age, histological differentiation, performance status, T/ N stages, and localization of primary tumor were independent prognostic factors of OS in stage III. Conclusions: S-AVANT confirms the initial AVANT report. No benefit of the bevacizumab addition to FOLFOX4 adjuvant therapy in patients with stage III CC was observed in terms of DFS with a negative effect in OS, without increase in non-CC related deaths. Clinical trial identification: NCT00112918. ? 2019 European Society for Medical Oncology
Subjects
adjuvant; bevacizumab; colon cancer; FOLFOX; XELOX
SDGs
Other Subjects
bevacizumab; capecitabine; fluorouracil; folinic acid; oxaliplatin; antineoplastic agent; bevacizumab; fluorouracil; folinic acid; platinum complex; adult; aged; Article; cancer adjuvant therapy; cancer grading; cancer prognosis; cancer staging; cancer survival; colon cancer; colorectal cancer; comorbidity; controlled study; disease free survival; drug withdrawal; female; hazard ratio; human; long term care; major clinical study; male; monotherapy; overall survival; phase 3 clinical trial; primary tumor; priority journal; randomized controlled trial; sudden death; toxicity; treatment planning; adjuvant chemotherapy; clinical trial; colon tumor; pathology; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemotherapy, Adjuvant; Colonic Neoplasms; Disease-Free Survival; Fluorouracil; Humans; Leucovorin; Neoplasm Staging; Organoplatinum Compounds
Publisher
Elsevier Ltd
Type
journal article