Neoadjuvant chemotherapy with oxaliplatin and fluoropyrimidine versus up-front surgery for locally advanced colon cancer:the randomized,phase Ⅲ OPTICAL trial[
Neoadjuvant chemotherapy with oxaliplatin and fluoropyrimidine versus up-front surgery for locally advanced colon cancer:the randomized,phase Ⅲ OPTICAL trial[
Purpose The role of neoadjuvant chemotherapy(NAC)in colon cancer remains unclear.This trial investigated whether 3 months of modified infusional fluorouracil,leucovorin,and oxaliplatin(mFOLFOX6)or capecitabine and oxalipla-tin(CAPOX)as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery.Pa-tients and methods OPTICAL was a randomized,phase Ⅲ trial in patients with clinically staged locally advanced colon cancer(T3 with extramural spread into the mesocolic fat ≥5 mm or T4).Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX,followed by surgery and adjuvant chemotherapy(NAC group),or immediate surgery and the physician's choice of adjuvant chemotherapy(upfront surgery group).The primary end point was 3-year disease-free survival(DFS)assessed in the modified intention-to-treat(mITT)population.Results Between January 2016 and April 2021,of the 752 patients enrolled,744 patients were included in the mITT analysis(371 in the NAC group;373 in the upfront surgery group).At a median follow-up of 48.0 months(IQR,46.0-50.1),3-year DFS rates were 82.1％in the NAC group and 77.5％in the upfront surgery group(stratified hazard ratio[HR],0.74[95％CI,0.54 to 1.03]).The R0 resection was achieved in 98％of patients who underwent surgery in both groups.Com-pared with upfront surgery,NAC resulted in a 7％pathologic complete response rate(pCR),significantly lower rates of advanced tumor staging(pT3-4:77％v 94％),lymph node metastasis(pN1-2:31％v 46％),and potentially improved overall survival(stratified HR,0.44[95％CI,0.25 to 0.77]).Conclusion NAC with mFOLFOX6 or CAPOX did not show a signifi-cant DFS benefit.However,this neoadjuvant approach was safe,resulted in substantial pathologic downstaging,and ap-pears to be a viable therapeutic option for locally advanced colon cancer.
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