5561 - FOxTROT: an international randomised controlled trial in 1053 patients evaluating neoadjuvant chemotherapy (NAC) for colon cancer.

Background

NAC has an established role in many solid tumours but its utility has not previously been formally evaluated in colon cancer.

Methods

Pts with CT-staged T3-4 N0-2 M0 colon cancer were randomised in a 2:1 ratio to pre-and-postoperative (NAC/AC) or postoperative (control) FOLFOX chemotherapy. Total planned chemotherapy was the same in both arms, but NAC/AC pts received the first 6 weeks before surgery. Pts with RAS-wt tumours could be subrandomised 1:1 to receive 6 wks panitumumab or not with NAC; if not randomised, CapOx was permitted. The primary endpoint was freedom from recurrent/residual disease at 2 years. Secondary outcomes included histological response/downstaging, safety and mortality. Analyses were by intent-to-treat.

Results

1053 pts entered at 98 hospitals in the UK, Denmark and Sweden. Of 699 allocated NAC/AC, 674 (97%) started and 612 (88%) completed 6 wks NAC. 684/699 (97.8%) NAC/AC and 349/354 (98.6%) control pts had tumour surgery. Signs of obstruction developed before surgery in 20 (3%) NAC/AC and 3 (1%) control pts. 3/699 NAC/AC and 1/354 control pt died before surgery. Serious perioperative morbidity was lower after NAC: anastomotic leaks [3.6% (26/684) vs 8.0% (28/349)]; complications prolonging hospital stay and re-operations [4.3% (29/684) vs 6.7% (23/349)]. 30-day postop mortality was 0.4% (3/677) vs 0.6% (2/343). Stoma rate was 12% vs 9%, (p = 0.18). There was marked histological downstaging after NAC, with lower pT and pN-stage (both p < 0.0001). 25/699 (3.8%) NAC/AC pts had pCR and 32 (4.6%) had near-complete tumour regression (Dworak TRG2/ Modified RyanTRS1). Incomplete (R1/R2) resections were reduced: 4.8% (33/684) vs 9.1% (32/348), p = 0.01. Dukes’ stage C2/D was seen in 4% (29/677) vs 9% (32/348), p = 0.002. There was also a trend towards less recurrent/residual disease within 2 years: 98/699 vs 62/354, HR = 0.77 (95%CI 0.56-1.06), P = 0.11.

Conclusions

Six weeks NAC for operable primary colon cancer can be delivered safely, with improved perioperative morbidity and marked pathological downstaging including some pCRs. There is a trend toward better disease control at 2 years. Subgroup analyses including impact by MMR status and effect of panitumumab will be presented at the meeting.

Clinical trial identification

ISRCTN 87163246.

Editorial acknowledgement

Legal entity responsible for the study

University of Birmingham.

Funding

Primary funder Cancer Research UK; Additional support: Amgen Pharma.

Disclosure

The author has declared no conflicts of interest.