Efficacy And Safety Of Two Neoadjuvant Strategies With Bevacizumab In Mri-Defined Locally Advanced T3 Resectable Rectal Cancer: Final Results Of A Randomized, Non Comparative Phase Ii 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 MRI-defined high risk LARC were randomized to Arm A (12-week bevacizumab + Folfox-4 then bevacizumab–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-year follow-up (FU) are reported. No comparison between the arms was planned. Results Overall, 91 patients (Arm A: 46; Arm B: 45) were included. Main results were presented previously. During the late FU period (>4 weeks after the surgery), 4 (8.7%) patients in Arm A and 4 (8.9%) Arm B experienced grade 3-4 adverse events related to bevacizumab, the most frequent were 2 anastomotic fistulas in Arm A and abscesses (Arm A, n=1; Arm B, n=2). At 5-year FU, 9 patients (19.6%) and 11 (24.4%) in Arms A and B developed a fistula in the year following surgery, and 2 (4.3%) in Arm A, > one year post-surgery. Most resolved before study end. 5-year DFS were 70% and 64.3% in Arms A and B, respectively. 5-year OS were 90.5% [95% CI 76.7, 96.3] in Arm A, and 72.7% [95% CI 56.0, 83.9] in Arm B. Conclusions Neo-adjuvant bevacizumab-Folfox-4 may have the potential to increase survival outcomes when followed with bevacizumab-5-FU-RT and TME in LARC. Bevacizumab-5-FU-RT then TME was associated with a higher rate of anastomotic fistulas than projected. Further research of neoadjuvant strategies in LARC is encouraged.