Neoadjuvant Chemotherapy With Oxaliplatin and Fluoropyrimidine Versus Upfront Surgery for Locally Advanced Colon Cancer: The Randomized, Phase III OPTICAL Trial
Authors: Hu Huabin , Zhang Jianwei , Li Yunfeng , Wang Xiaozhong , Wang Ziqiang , Wang Hui , Kang Liang , Liu Ping , Lan Ping , Wu Xiaojian , Zhen Yunhuan , Pei Haiping , Huang Zhongcheng , Zhang Hao , Chen Wenbin , Zeng Yongming , Lai Jiajun , Wei Hongbo , Huang Xuefeng , Chen Jiansi , Chen Jigui , Tao Kaixiong , Xu Qingwen , Peng Xiang , Liang Junlin , Cai Guanfu , Ding Kefeng , Ding Zhijie , Hu Ming , Zhang Wei , Tang Bo , Hong Chuyuan , Cao Jie , Huang Zonghai , Cao Wuteng , Li Fangqian , Wang Xinhua , Wang Chao , Huang Yan , Zhao Yandong , Cai Yue , Ling Jiayu , Xie Xiaoyu , Wu Zehua , Shi Lishuo , Ling Li , Liu Hao , Wang Jianping , Huang Meijin , Deng Yanhong ,   on behalf of the OPTICAL study group, Deng Yanhong , Li Yunfeng , Wang Ziqiang , Wang Xiaozhong , Zhang Ruyi , Pei Haiping , Huang Zhongcheng , Zhang Hao , Chen Wenbin , Zeng Yongming , Lai Jiajun , Wei Hongbo , Huang Xuefeng , Chen Jiansi , Chen Jigui , Tao Kaixiong , Xu Qingwen , Peng Xiang , Liang Junlin , Cai Guanfu , Ding Kefeng , Ding Zhijie , Hu Ming , Zhang Wei , Tang Bo , Hong Chuyuan , Cao Jie , Huang Zonghai 
Published: April 2024

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 oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery.

PATIENTS 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. Compared 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 significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.