Potential Benefits From Neoadjuvant Chemotherapy for Patients With Locally Advanced Colon Cancer

Results from the phase 3 OPTICAL study demonstrated that while neoadjuvant chemotherapy with modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) did not significantly improve disease-free survival rates when compared to adjuvant chemotherapy among patients with locally advanced colon cancer, there are some potential benefits.

“Neoadjuvant chemotherapy has the potential to shrink tumors and reduce the risk of incomplete resection and tumor cell shedding… however the role of neoadjuvant chemotherapy in colon cancer remains unclear,” stated Huabin Hu, MD, Sun Yat-Sen University, Guangzhou, China, and coauthors. 

In this multicenter study, 744 patients with locally advanced colon cancer were randomized on a 1-to-1 basis to receive either neoadjuvant (n = 373) or adjuvant (n = 373) mFOLFOX6 or CAPOX. The primary end point was the 3-year disease-free survival (DFS) rate. Secondary end points included 3-year overall survival (OS) rate, R0 resection, pathologic complete response (pCR) rate, and safety. 

At a median follow-up of 48 months, the 3-year DFS rate was 82.1% in the neoadjuvant arm and 77.5% in the adjuvant arm (stratified hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.54 to 1.03; log-rank P = .07) and 3-year OS rate was 95.1% in the neoadjuvant arm and 89.6% in the adjuvant arm (stratified HR, 0.44; 95% CI, 0.25 to 0.77; log-rank P = .01). In both treatment arms, 98% of patients who underwent surgical resection achieved R0 resection. In the neoadjuvant arm, pCR rate was 7%. Grade ≥3 adverse events occurred in 29% of patients in the neoadjuvant arm. The most common events included neutropenia (16%) and anemia (11%) among patients who received mFOLFOX6, and anemia (9%) and hand-foot syndrome (5%) among patients who received CAPOX.

Though neoadjuvant chemotherapy with mFOLFOX6 or CAPOX did not show a significant DFS benefit, it “resulted in substantial pathologic tumor regression, disease downstaging, and potentially improved overall survival, without safety concerns," concluded Dr Hu et al. They noted this approach “appears to be a viable therapeutic option for locally advanced colon cancer.” 

“This study adds to the growing body of literature demonstrating not only the safety but also some potential benefits of this approach when compared to up-front surgery,” added Journal of Clinical Oncology associate editor, Andrew H. Ko, MD, University of California, San Francisco. 

Source: 

Hu H, Zhang J, Li Y, et al. Neoadjuvant chemotherapy with oxaliplatin and fluoropyrimidine versus upfront surgery for locally advanced colon cancer: The randomized, phase III OPTICAL trial. J Clin Oncol. Published online: April 2, 2024. doi:10.1200/JCO.23.01889