FOxTROT: an international randomised controlled trial in 1052 patients (pts) evaluating neoadjuvant chemotherapy (NAC) for colon cancer.

Abstract

3504 Background: NAC is well established in many solid tumours but has not undergone large-scale evaluation in colon cancer. Methods: Pts had operable, non-obstructed colon cancer; CT-predicted stage T3-4, N0-2, M0, and were fit for FOLFOX and surgery. They were randomised 2:1 to the novel sequence (6 wk FOLFOX NAC, then surgery, then 18 wk FOLFOX) or control (surgery then 24 wk FOLFOX). RAS-wt pts allocated to the novel arm could optionally be sub-randomized 1:1 to ± panitumumab (pan) during the NAC phase. Two "dealer’s choices" allowed total chemo duration 12 wk instead of 24 (in older/low-risk pts) and OxCap in place of FOLFOX (except in pts randomized ± pan). Primary endpoint is freedom from recurrent or persistent disease after 2 yrs, by ITT. Secondary endpoints include safety, histological stage, completeness of resection, OS. Results: 1052 pts were randomised, Jun 2008-Dec 2016, at 85 centres in UK, Denmark and Sweden. Conclusions: NAC was well tolerated and safe, with no increase in perioperative morbidity and a trend toward fewer serious postoperative complications. Evidence of histological regression was seen in 59% pts after NAC, including some pCRs. This resulted in marked histological downstaging and a halving of the rate of incomplete resections. We observed an improvement in 2-yr failure rate (HR=0.77), but this fell short of statistical significance (p=0.11). NAC for colon cancer improves surgical outcomes and can now be considered as a treatment option; longer follow-up and further trials are required to confirm the long-term benefits, refine its use and optimise case selection. Clinical trial information: 87163246. [Table: see text]