FOxTROT: neoadjuvant FOLFOX chemotherapy with or without panitumumab (Pan) for patients (pts) with locally advanced colon cancer (CC).

4013 Background: FOxTROT has reported marked down-staging, reduced perioperative morbidity and a trend towards fewer recurrences with 6 wks of oxaliplatin-fluoropyrimidine neoadjuvant chemotherapy (NAC) in CC (Seymour, ASCO 2019 abstract 3504). Using updated data, we investigate the contribution of panitumumab (Pan) and tumour markers to efficacy of NAC. Methods: 1053 pts with radiologically-staged T3-4, N0-2, M0 CC were randomly allocated (2:1) to either 6 wks of NAC and 18 wks of postoperative adjuvant chemotherapy (AC) or 24 wks of AC. 279 pts with RAS-wt tumours were also randomised 1:1 to receive Pan or not with NAC. The primary endpoint was freedom from recurrence or residual disease at 2 years for NAC vs AC, and depth of extramural spread for the Pan randomisation; secondary endpoints include safety, histological downstaging, CC-specific survival and OS. Results: Of 699 allocated pre-and-postoperative chemotherapy, 674 (97%) started and 612 (88%) completed NAC. 684/699 (97.8%) pre-and-postoperative and 349/354 (98.6%) control patients underwent tumour resection. There was marked T- and N-down-staging and tumour regression with NAC (all p<0.001). There were fewer disease recurrences within 2 years in the NAC than AC group: 15.6% (109/698) vs 19.5% (69/354), RR=0.76 (95%CI 0.56-1.02), P=0.07. Response to NAC was significantly (p<0.001) less in MMR-deficient (dMMR) than MMR-proficient (pMMR) tumours: 7%(8/115) vs 23%(128/553) moderate or greater histological tumour regression. Reductions in 2-year recurrence were also seen only in pMMR tumours [RR=0.72 (0.52-1.00), p=0.05], with no apparent benefit in dMMR tumours: RR=0.94 (0.43 to 2.07), p=0.9]. Analyses of panitumumab will be presented. Conclusions: Six weeks of NAC for operable CC can be delivered safely, with marked histopathological down-staging, and may result in better disease control at 2 years in pMMR disease. Clinical trial information: 87163246 .