Background
Phase III RCT of 1052 randomized patients (699 in the main comparison) with radiologically staged T3-4, N0-2, M0 colon cancer. Patients with bowel obstruction were eligible if defunctioned with a stoma.
Interventions and follow up
Arm A (neoadjuvant): mFOLFOX (fluorouracil 400 mg/m2 bolus + 2400 mg/m2 46-h infusion, oxaliplatin 85 mg/m2) Q2W x12 cycles (3 neoadjuvant + 9 adjuvant); RAS wild-type patients sub-randomized to panitumumab 6 mg/kg during cycles 1-3
Arm B (control): Surgery followed by adjuvant chemotherapy
Primary endpoint: Residual or recurrent disease (RRD) at 2 years
mFollow up: 3.1 years
Arm B (control): Surgery followed by adjuvant chemotherapy
Primary endpoint: Residual or recurrent disease (RRD) at 2 years
mFollow up: 3.1 years
Results
2-yr RRD: 6.9% (Arm A) vs 21.5% (Arm B); rate ratio 0.72, 95% CI 0.54–0.98; P=.037
Pathologic downstaging: Significantly higher with neoadjuvant therapy; complete pathologic response in approximately 4%
R0 resection: Higher rate of histologically complete resection in the neoadjuvant arm
Pathologic downstaging: Significantly higher with neoadjuvant therapy; complete pathologic response in approximately 4%
R0 resection: Higher rate of histologically complete resection in the neoadjuvant arm
Adverse events
Surgical (A vs B): Anastomotic leak or abdominal abscess 4.7% vs 7.4%, P=.072; emergency reoperation 4.3% vs 7.1%, P=.05
Overall tolerability: Neoadjuvant chemotherapy was tolerable with rare serious toxicity; postoperative morbidity and 30-day mortality were similar between arms
Overall tolerability: Neoadjuvant chemotherapy was tolerable with rare serious toxicity; postoperative morbidity and 30-day mortality were similar between arms
Conclusions
In patients with operable, locally advanced colon cancer, neoadjuvant FOLFOX improved 2-year disease control without increasing surgical complications. Addition of panitumumab in RAS wild-type patients did not improve outcomes.
Key Limitations
Radiologic staging may misclassify T-stage, risking overtreatment of earlier disease; modest absolute RRD difference; longer-term DFS/OS maturing; no benefit from panitumumab sub-randomization.
Clinical Context
FOXTROT provides proof of concept for neoadjuvant chemotherapy in locally advanced colon cancer but has not displaced upfront surgery as the default standard; ESMO regards neoadjuvant chemotherapy as an option in selected radiologically high-risk (T4) tumors. Accurate pretreatment staging and avoidance of overtreatment are central considerations.