Safety and efficacy of neoadjuvant chemotherapy (NAC) in older patients with locally advanced colon cancer (LACC): Results from FOxTROT 1 and the FOxTROT 2 safety cohort population.

3653 Background: The FOxTROT1 (FT1; NCT00647530) trial demonstrated feasibility and efficacy of six weeks of NAC for LACC compared with upfront surgery. The currently recruiting FOxTROT2 trial (ISRCTN83842641) is testing this approach in older or frail patients. Outcomes in older patients with LACC are inferior; therefore, new treatment strategies are required. Here in these trials we analyse the safety and efficacy of NAC in this group and report the DFS in the older subgroup of FT1 PMMR patients. Methods: Data from FT1 and the planned FT2 safety pilot (n=150) were combined and analysed by treatment arm and by age category (</> 70). Pre-specified endpoints included NAC delivery and perioperative complication rates for FT1 and FT2; DFS and pathological response are reported for FT1 patients by MMR status. We will update safety data for this presentation. Results: In FT1 292/1052 (27.8%) of patients were aged over 70; the median age of FT2 safety cohort was 76 (range 70-85). There were no significant differences by age in NAC delivery or in rates of peri-operative complications. For patients over 70, combining FT1&2 data, exploring those who received NAC, 88.5% completed the course as planned and 37.7% received an upfront or subsequent dose modification. Rates of peri-operative complications combining FT1&2 were similar between patients receiving NAC or upfront surgery: anastomotic leak (3.4% vs 3.3%), complication requiring hospital stay (FT1 9.3% vs 14.6%) or further surgery (2.6% vs 5.0%), and post-operative death (0.9 % vs 1.7%). For patients over 70 in FT1 16.4% were dMMR and 83.6% were pMMR. In pMMR patients overall NAC improved 3-year DFS (81.2% vs 75.4% without a DFS event; HR 0.70[0.52–0.94],p=0.02) compared with upfront surgery; results were consistent in older patients (81.2% vs 71.4%; HR 0.59[0.35-1.02],p=0.06). Conclusions: NAC is safe and well-tolerated in older adults, with no increase in perioperative morbidity and preserved treatment delivery compared to rates in younger patients and when compared with upfront surgery. Promising efficacy in terms of 3-year DFS and pathological response were observed in older patients with pMMR tumors, consistent to those seen in younger patients. These data support the use of NAC in older patients with LACC and continued recruitment to FT2 to evaluate the long term impact. Clinical trial information: NCT00647530 .