FOxTROT: an international randomised controlled trial in 1052 patients evaluating neoadjuvant chemotherapy for colon cancer
Session type: Clinical Trials Showcase
Preoperative chemotherapy is beneficial in many solid cancers but not previously investigated in colon cancer.
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.
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.
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.