Efficacy and Safety of Two Neoadjuvant Strategies With Bevacizumab in MRI-Defined Locally Advanced T3 Resectable Rectal Cancer: Final Results of a Randomized, Noncomparative Phase 2 INOVA Study.

Abstract

BACKGROUND:

Recurrence and distant metastases remain a significant issue in locally advanced rectal cancer (LARC). Several multimodal strategies are assessed in clinical trials.

PATIENTS AND METHODS:

Patients with mid/low magnetic resonance imaging-defined high-risk LARC were randomized to arm A (12-week bevacizumab + FOLFOX-4 then bevacizumab-5-fluorouracil [5-FU]-radiotherapy [RT] before total mesorectal excision [TME]) or arm B (bevacizumab-5-FU-RT then TME). Long-term efficacy and safety up to 5 years' follow-up are reported. No comparison between arms was planned.

RESULTS:

Overall, 91 patients (46 in arm A and 45 in arm B) were included. Main results have been presented previously. During the late follow-up period (> 4 weeks after surgery), 4 patients (8.7%) in arm A and 4 (8.9%) in arm B experienced grade 3/4 adverse events related to bevacizumab; the most frequent were 2 anastomotic fistulas (both in arm A) and abscesses (1 in arm A and 2 in arm B). At 5 years' follow-up, 9 (19.6%) and 11 (24.4%) patients in arms A and B developed a fistula in the year after surgery, and 2 (4.3%) in arm A at > 1 year after surgery. Most resolved before study end. Five-year disease-free survival was 70% and 64.3% in arms A and B, respectively. Five-year overall survival was 90.5% (95% confidence interval, 76.7, 96.3) in arm A and 72.7% (95% confidence interval, 56.0, 83.9) in arm B.

CONCLUSION:

Neoadjuvant bevacizumab + FOLFOX-4 may have the potential to increase survival outcomes when followed by bevacizumab-5-FU-RT and TME in LARC. Bevacizumab-5-FU-RT then TME was associated with a higher-than-projected rate of anastomotic fistulas. Further research of neoadjuvant strategies in LARC is encouraged.

• Authors: Christophe Borg, Georges Mantion, Frank Boudghène, Françoise Mornex, François Ghiringhelli, Antoine Adenis, David Azria, Jacques Balosso, Meher Ben Abdelghani, Jean Baptiste Bachet, Véronique Vendrely, Yves François, Thierry Conroy, Emmanuel Rio, Bernard Roullet, Dominique Spaëth, Laurent Quero, Zaher Lakkis, Mathieu Coudert, Miruna Ionescu-Goga, Alexandre Tanang, Thierry André
• Journal: Clinical colorectal cancer (Clin Colorectal Cancer) Vol. 18 Issue 3 Pg. 200-208.e1 (09 2019) ISSN: 1938-0674 [Electronic] United States
• PMID: 31311761 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• Oxaliplatin
• Bevacizumab
• Capecitabine
• Leucovorin
• Fluorouracil

Topics

• Adenocarcinoma (drug therapy, pathology, radiotherapy, surgery)
• Adolescent
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bevacizumab (administration & dosage)
• Capecitabine (administration & dosage)
• Chemoradiotherapy, Adjuvant
• Female
• Fluorouracil (administration & dosage)
• Follow-Up Studies
• Humans
• Leucovorin (administration & dosage)
• Lymphatic Metastasis
• Magnetic Resonance Imaging (methods)
• Male
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Recurrence, Local (drug therapy, pathology)
• Oxaliplatin (administration & dosage)
• Rectal Neoplasms (drug therapy, pathology, radiotherapy, surgery)
• Survival Rate
• Young Adult