411P A randomized, open-label, parallel-design phase III study to compare adjuvant 5-FU plus oxaliplatin (mFLOX) versus observation in locally advanced rectal cancer after neoadjuvant chemoradiation

Based on the known advantages of adjuvant chemotherapy for stage III colon cancer, the addition of oxaliplatin and 5-fluorouracil (5-FU) for resected rectal adenocarcinoma post neoadjuvant chemoradiation (CRT) has been discussed extensively in the literature. In this study, we investigated the role of postoperative adjuvant 5-FU and oxaliplatin (mFLOX) chemotherapy in this scenario. Eligible patients had T3-4 or N+ rectal adenocarcinoma, post fluoropyrimidine-based CRT and curative resection. They were randomized to observation or 2 cycles of mFLOX. The primary endpoint was disease free survival (DFS); secondary endpoints were toxicities and overall survival (OS). A total of 309 patients were planned to detect a 30% difference between the groups, with 80% power and a one-sided alpha of 5%. After 8 years of recruitment, the study was closed prematurely in 2019 due to slow accrual. A total of 133 patients were included and assigned to observation (n = 78) or mFLOX (n = 55). 42 (76,4%) patients completed the study treatment as planned. 17 patients withdrew informed consent. Main toxicities (grade 3/4) in the group assigned to treatment were diarrhoea (12%), thrombocytopenia (6%) and lymphopenia (13%). After a median follow-up of 63 months, 29 (37,2%) patients in the observation arm had relapsed or died compared with 23 (41,8%) patients in the mFLOX group. The 5-year DFS rates were 70,5% in the mFLOX and 70,4% in the observation group [hazard ratio (HR) for DFS = 1,221; 95% confidence interval (CI) 0,700 - 2,129; P = 0,482]. The 5-year OS for mFLOX and the observation group were 77,5% and 79,3%, respectively [HR for OS = 1,295; 95% CI 0,629 - 2,664; P = 0,483]. Despite the study being prematurely closed, no difference was observed in DFS or OS for patients treated with adjuvant chemotherapy containing 5FU plus oxaliplatin compared to the observation after neoadjuvant CRT and surgery.