1. 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
- Author
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Emmanuel Rio, Christophe Borg, François Ghiringhelli, Mathieu Coudert, Meher Ben Abdelghani, Yves François, Françoise Mornex, Alexandre Tanang, Thierry Conroy, Bernard Roullet, Frank Boudghène, Laurent Quero, Véronique Vendrely, Dominique Spaeth, Antoine Adenis, Thierry André, Miruna Ionescu-Goga, D. Azria, Zaher Lakkis, Jean-Baptiste Bachet, Jacques Balosso, Georges Mantion, Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Médecine Nucléaire, Centre Georges-François Leclerc [Dijon] (CGFL), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Institut du Cancer de Montpellier (ICM), Centre Paul Strauss, CRLCC Paul Strauss, Service d'oncologie médicale [ICL Alexis Vautrin], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Oncologie médicale [Polyclinique de Gentilly, Nancy], Polyclinique de Gentilly, Roche France, Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Bevacizumab ,Colorectal cancer ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,Leucovorin ,Adenocarcinoma ,Anastomosis ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Adverse effect ,Capecitabine ,Aged ,Rectal Neoplasms ,business.industry ,Gastroenterology ,Chemoradiotherapy, Adjuvant ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Total mesorectal excision ,Neoadjuvant Therapy ,Confidence interval ,3. Good health ,Surgery ,Oxaliplatin ,Survival Rate ,Radiation therapy ,Clinical trial ,Oncology ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Fluorouracil ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies ,medicine.drug - 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.
- Published
- 2019