ELECLA trial: final results of perioperative chemotherapy with fluoropyrimidine and oxaliplatin in mismatch repair proficient locally advanced colon cancer.

Abstract

The current standard of care for resectable locally advanced colon cancer (LACC) is based on upfront surgery followed by adjuvant chemotherapy (AC). This study aimed to evaluate the safety and efficacy of neoadjuvant chemotherapy (NAC) in this setting. ELECLA is a multicenter, randomized, open-label, phase II controlled trial conducted across 12 hospitals in Spain between March 2017 and June 2024. This report presents the results of a preplanned interim analysis conducted after early termination of recruitment following the loss of clinical equipoise. Patients with radiologically defined LACC (T3 > 5 mm/T4, any N, and M0) and proficient mismatch repair status, were randomly assigned at a 1:1 ratio to receive either NAC (three cycles of CAPOX or five of FOLFOX), surgery, and AC (investigational group) or upfront surgery followed by AC (control group). The primary endpoint was 2-year disease-free survival. A total of 120 patients were included. The NAC completion rate was 94.2%, with a nonsignificant trend toward a reduced surgical complication rate compared with controls (17.3% versus 22.1%; P = 0.52). In the investigational group, a favorable radiologic tumor downstaging was achieved, with a tumor volume reduction of 65.4% (P < 0.001), and a tumor regression grading of 0-2 in 51.2% of assessable patients. An R0 resection was achieved in all patients within the NAC group. A relevant reduction in classical histological adverse prognostic features, including lymphatic invasion (21.5% versus 44.1%; P = 0.009), tumor budding (23.3% versus 58.5%; P = 0.002), and incomplete resections (0% versus 7.4%; P = 0.068) was observed in the NAC group. The 2-year disease-free survival rate was 88.9% [95% confidence interval (CI) 75.2% to 95.2%] in the intervention group and 83.3% (95% CI 70.9% to 90.7%) in the control group (P = 0.34). NAC is safe, feasible, and associated with improved tumor downstaging and favorable pathologic features without increased perioperative morbidity. These findings support the use of NAC as a safe and efficient therapeutic option in patients with LACC.