Does neoadjuvant FOLFOX chemotherapy improve the prognosis of high‐risk Stage II and III colon cancers? Three years' follow‐up results of the PRODIGE 22 phase II randomized multicentre trial

Abstract

Background Neoadjuvant chemotherapy has proven valuable in locally advanced resectable colon cancer (CC) but its effect on oncological outcomes is uncertain. We report the 3‐year oncological outcomes of the PRODIGE 22 trial. Patients‐Methods PRODIGE 22 was a randomized multicenter phase II trial in high‐risk T3, T4 and/or N2 CC patients on CT‐scan. Patients were randomized between 6 months of adjuvant FOLFOX (upfront surgery) or perioperative FOLFOX (4 cycles before surgery and 8 cycles after) (FOLFOX peri‐op). In RAS WT patients, a third arm testing perioperative FOLFOX‐cetuximab was added. Primary endpoint was the Tumour Regression Grade. Secondary endpoints were 3‐year overall survival (OS), disease‐free survival (DFS), recurrence‐free survival (RFS) and time to recurrence (TTR). Results Overall 120 patients were enrolled. At interim analysis, the FOLFOX‐cetuximab arm was stopped for futility. The remaining 104 patients represented our intention‐to‐treat population. In the peri‐op group, 96% received the scheduled neoadjuvant 4 cycles and all but one had adjuvant FOLFOX for 8 cycles. In the control arm, 38 (73%) patients received adjuvant FOLFOX. The median follow‐up was 54.3 months. Three‐year OS was 90.4% in both arms (HR=0.85), 3‐year DFS, RFS and TTR was 76.8% and 69.2% (HR=0.94), 73% and 69.2% (HR=0.86) and 82% and 72% (HR=0.67) in the peri‐op and control arm respectively. Forest‐plot did not show any subgroup with significant difference for survival outcomes. No benefit from adding cetuximab was observed. Conclusion Perioperative FOLFOX has no detrimental effect on long‐term oncological outcomes and may be an option for some patients with locally advanced CC.