Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, People's Republic of China.
J Clin Oncol. 2024 Sep 1;42(25):2978-2988. doi: 10.1200/JCO.23.01889. Epub 2024 Apr 2.
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.
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.
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% 94%), lymph node metastasis (pN1-2: 31% 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]).
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.
新辅助化疗（NAC）在结肠癌中的作用仍不清楚。本试验旨在研究 3 个月改良持续输注氟尿嘧啶、亚叶酸钙和奥沙利铂（mFOLFOX6）或卡培他滨和奥沙利铂（CAPOX）作为 NAC 是否可以改善局部晚期结肠癌患者的结局，与直接手术相比。
OPTICAL 是一项在临床分期为局部晚期结肠癌（T3 伴有外膜扩散至系膜脂肪≥5mm 或 T4）患者中进行的随机、III 期试验。患者按 1:1 随机分配接受术前 6 个周期的 mFOLFOX6 或 4 个周期的 CAPOX，然后进行手术和辅助化疗（NAC 组），或直接手术和医生选择的辅助化疗（直接手术组）。主要终点是改良意向治疗（mITT）人群中的 3 年无病生存（DFS）。
2016 年 1 月至 2021 年 4 月期间，共纳入 752 例患者，744 例患者纳入 mITT 分析（NAC 组 371 例，直接手术组 373 例）。中位随访 48.0 个月（IQR，46.0-50.1）时，NAC 组和直接手术组的 3 年 DFS 率分别为 82.1%和 77.5%（分层风险比[HR]，0.74[95%CI，0.54 至 1.03]）。两组均有 98%的手术患者达到 R0 切除。与直接手术相比，NAC 可使病理完全缓解率（pCR）提高 7%，肿瘤分期更高（pT3-4：77% 94%）、淋巴结转移（pN1-2：31% 46%）的比例更低，且总生存（分层 HR，0.44[95%CI，0.25 至 0.77]）可能得到改善。
mFOLFOX6 或 CAPOX 联合 NAC 并未显示出显著的 DFS 获益。然而，这种新辅助方法是安全的，可显著降低肿瘤分期，并可能成为局部晚期结肠癌的一种可行的治疗选择。
