FOxTROT: an international randomised controlled trial in 1052 patients evaluating neoadjuvant chemotherapy for colon cancer


Year:

Session type:

Theme:

Dion Morton, on behalf of the FOxTROT investigators1
1University of Birmingham, Birmingham, UK

Abstract

Background

Preoperative chemotherapy is beneficial in many solid cancers but not previously investigated in colon cancer.

Method

Patients with operable, non-obstructed colon cancer, CT-predicted T≥3 Nx M0, were randomised 2:1 to pre&postop (6 weeks chemotherapy; surgery; completion of chemotherapy) or postop (surgery then chemotherapy). KRAS-wt patients could optionally be subrandomised 1:1 to ± panitumumab with preop chemotherapy. In two "dealers' choices", clinicians selected the chemotherapy schedule (FOLFOX 72%; CapOx 28%) and total planned chemo duration (24 weeks 94%; 12 weeks 6%). Primary endpoint is freedom from recurrent or persistent disease to 2 yrs, by ITT. Secondary endpoints include safety, histological stage, completeness of resection. A sensitivity analysis assessed the contribution of panitumumab. A single exploratory subgroup analysis was conducted for pMMR/uk (83.6%) vs dMMR (16.4%) cancers.

Results

1052 patients entered in the UK and Scandinavia, median age 65; right:left colon 49:51%.

Pre&post n=698Postop n=354went for surgery...98.2%97.7%...of whom: re-operation for postop morbidity4.3%7.1%p=0.05                  R1, R2 or failure to resect4.8%11.1%p<0.001relapse/persistent cancer at 2 yrs13.6%17.2%HR=0.75 2p=0.08T-stage at surgery: ≤2/3/4 (%)15.8/63.7/20.55.8/64.5/29.8p<0.0001 N-stage at surgery: 0/1/2 (%)59.4/25.4/15.2 48.8/25.1/25.9p<0.0001Tumour regression grade: 0/1/2-4 (%)33.9/43.9/19.978.8/17.7/0.6p<0.0001

The sensitivity analysis shows no evidence that panitumumab has contributed to the overall benefits seen in the pre&postop arm. In the subgroup analysis, minimal response to preoperative chemotherapy was seen in MMR tumours, but interaction testing is non-significant.

Conclusion

FOxTROT fell just short of statistical significance for its primary endpoint of 2-year disease control (HR=0.75, 2p=0.08); however, highly significant benefits were seen in terms of reduced postop morbidity, fewer failed or margin-positive resections and marked histological downstaging. This approach may therefore be considered a new treatment option for discussion with patients. Minimal benefit was apparent in dMMR cancers.

© 2019 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2019 ASCO Annual Meeting. All rights reserved.