Phase II trial of induction mFOLFOX6 plus bevacizumab followed by neoadjuvant S-1-based chemoradiation for MRI-defined poor-risk rectal cancer.

Abstract

700 Background: Induction chemotherapy has been explored as a novel treatment option to improve oncological outcomes in poor-risk locally advanced rectal cancer (LARC). Although previous studies have suggested high pCR rate with a favorable toxicity profile in S-1-based neoadjuvant chemoradiation, no study has evaluated induction chemotherapy added with this regimen. The present study is designed to evaluate the safety and efficacy of induction chemotherapy with bevacizumab followed by neoadjuvant S-1 based chemoradiation in MRI-defined poor-risk LARC. Methods: This was a single-center phase II trial at a high-volume cancer center. Eligible patients had low rectal adenocarcinoma with MRI-defined poor-risk features. Patients received 12-week (6 course) mFOLFOX plus bevacizumab (5 mg/kg every 2 weeks) followed by concomitant oral S-1 (80mg/m2/day on days 1-5, 8-12, 22-27, and 29-33) plus radiotherapy (50.4Gy). Surgery was scheduled for 6-10 weeks after chemoradiation. Pathological complete response (pCR) was the primary endpoint. Results: A total of 43 eligible patients were enrolled. Forty-two patients (98%) completed induction chemotherapy. Forty-two patients (98%) completed planned radiation dose. One patient with cCR after completion of preoperative treatment declined surgery, but all the other 42 patients (98%) underwent R0 resection thorough a laparoscopic approach. A pCR was achieved in 16 patients (37%; 95% confidence interval 24.4%-52.1%). CTCAE grade 3 adverse events (AEs) occurred in 4 patients (9.3%) during induction chemotherapy and 5 patients (12%) during chemoradiation. There were no grade 4 AEs. Clavien-Dindo Classification grade III-IV surgical complications occurred in 6 patients (14%), including 1 grade IVa delirium, 1 grade IIIb anastomotic leakage, 1 grade IIIb bleeding, 2 grade IIIa pelvic abscess and 1 grade IIIa urethral fistula. There was no mortality. Conclusions: Induction FOLFOX plus bevacizumab followed by S-1-based chemoradiation achieved a high pCR rate with favorable toxicity and tolerable surgical complications in poor-risk LARC. Phase III trial is needed for further evaluation. Clinical trial information: UMIN000011457.