CapeOX Versus Capecitabine in Neoadjuvant Chemoradiation for High-Risk Locally Advanced Rectal Cancer: Long-Term Results From the MONT-R Randomized Controlled Trial.

PURPOSE: The clinical benefit of incorporating oxaliplatin into conventional neoadjuvant chemoradiotherapy (nCRT) for patients with high-risk locally advanced rectal cancer (LARC) remains controversial.

METHODS AND MATERIALS: This multicenter, open-label, randomized controlled trial enrolled 505 patients with high-risk LARC, defined by the presence of at least 1 of the following adverse features: clinical T4 stage, clinical N2 stage, high tumor grade, extramural vascular invasion, involvement of the mesorectal fascia, or perianal musculature involvement. Enrollment took place between August 2017 and April 2022. Patients were randomly assigned to receive long-course radiation therapy combined with a 3-cycle chemotherapy regimen of capecitabine and oxaliplatin (CapeOX group; n = 248) or capecitabine alone (Cape group; n = 257). The primary endpoint was 3-year disease-free survival (3y-DFS).

RESULTS

Following nCRT, radical surgery was performed in 91.5% of the CapeOX group and 92.2% in the Cape group (P = .778). Pathologic complete response rates were comparable between the CapeOX and Cape groups (25.5% vs 25.3%; P = .954). A significantly greater proportion of patients in the CapeOX group achieved marked tumor regression (College of American Pathologists (CAP 0-1)) compared with the Cape group (58.6% vs 46.8%; P = .011). The incidence of grade 3 to 4 treatment-related toxicities was similar between the groups (CapeOX: 14.1% vs Cape: 9.3%; P = .095). After a median follow-up of 37 months, 3y-DFS and 3-year overall survival rates were comparable between the groups (both P > .050). Overall, patients who achieved CAP 0 to 1 had significantly better 3y-DFS than those with CAP 2 to 3 (89.0% vs 80.9%; P = .018).

CONCLUSIONS

The addition of oxaliplatin to conventional nCRT may enhance pathologic tumor regression in patients with high-risk LARC without a significant increase in severe adverse events. However, this intensified 3-cycle chemotherapy regimen did not translate into a long-term survival benefit.