Phase III randomized clinical trial comparing the efficacy of neoadjuvant chemotherapy and standard treatment in patients with locally advanced colon cancer: The NeoCol trial.

Abstract

LBA3503 Background: Locally advanced colon cancer presents a therapeutic challenge regarding improving survival and minimizing side effects by optimizing the timing of surgical and systemic treatments. Neoadjuvant chemotherapy is a widely accepted approach in numerous cancers as it aims to eliminate micrometastases and reduce tumor size. Our study aimed to assess the impact of neoadjuvant chemotherapy on locally advanced colon cancer compared to standard initial surgery. Methods: This was a randomized, controlled, phase III clinical trial. Patients aged 18 years or older with biopsy-proven colon cancer were eligible for inclusion if staged as T4 or T3 with invasion depth ≥5 mm, N0-2, and M0 according to CT scan evaluation. Patients were randomly assigned to either standard upfront surgery or surgery after neoadjuvant chemotherapy with either 3 cycles of CAPOX (oxaliplatin, capecitabine every 3 weeks) or 4 cycles of FOLFOX (oxaliplatin, 5FU every 2 weeks). Adjuvant chemotherapy was chosen based on the pathological stage of the cancer according to guidelines. The primary endpoint, disease-free survival (DFS), was analyzed on an intent-to-treat basis. The sample size was set at 125 patients per arm, based on a projected increase in two-year disease-free survival from 80% to 90%, with a two-sided significance level of 5%, power of 80%, 3 years of inclusion, 2 years of follow-up, and a 10% drop-out rate. Results: Nine centers in 3 countries included 122 patients in the standard group and 126 patients in the neoadjuvant group from 10/2013 to 11/2021. Forty-four % were female, the median age was 66 years, and 91% had a performance status (PS) of 0, while 9% had a PS of 1. Seventy-three % of the tumors were classified as T3, with a median outgrowth of 11 mm, while 26% were classified as T4 on the baseline CT scan. There were no significant differences in baseline characteristics. The median number of chemotherapy cycles was lower in the neoadjuvant group, 3 (IQR 1-7) vs. 4 (0-8). There were slightly more postoperative complications in the standard group regarding ileus, anastomotic leakage, and length of stay. Postoperatively, more patients in the standard arm had an indication of adjuvant chemotherapy, 88 vs. 72 (p = 0.02). DFS at 2 years was similar in the two arms (p = 0.95, logrank), as was overall survival (OS) (p = 0.95, logrank). Conclusions: Neoadjuvant chemotherapy and standard upfront surgery showed no significant difference in DFS and OS in patients with colon cancer. However, neoadjuvant chemotherapy seemed to have more favorable outcomes in terms of chemotherapy cycles, postoperative complications, and downstaging. CT scan alone may not be sufficient in identifying high-risk patients preoperatively. These findings suggest that neoadjuvant chemotherapy could be considered a viable treatment option for patients with locally advanced colon cancer. Clinical trial information: NCT01918527 .

The ELECLA trial: A multicentre randomised control trial on outcomes of neoadjuvant treatment on locally advanced colon cancer

“…Recent meta‐analyses have indicated that neoadjuvant treatment improves long‐term surgical and oncological outcomes [28, 57, 58]; but the final role of NAC in LACC in the therapeutic guidelines remains unresolved [24, 44, 59–62]. This is the reason why the authors consider this topic worthy of continued research, as revealed by the ongoing FOxTROT2 and FOxTROT3, OPTICAL or NeoCol trials [63–65].…”

Survival and safety after neoadjuvant chemotherapy or upfront surgery for locally advanced colon cancer: meta-analysis

“…Over the course of the present study, two significant RCTs comparing NAC with upfront surgery in patients with LACC were presented at ASCO 2022 and 2023 Meeting, and were subsequently published in abstract form 33 , 34 . To maintain consistency with the inclusion/exclusion criteria of the present study, these trials were not included in the primary analysis.…”

Preoperative Strategies for Locally Advanced Colon Cancer

“…The Scandinavian NeoCol trial randomized 250 patients with T3 or T4 and N0-2 disease as assessed on CT scan to 3 cycles of CAPOX or FOLFOX prior to surgery versus standard of care with upfront surgery [ 11 ]. The data have been presented but not published.…”

“…Several randomized controlled trials of perioperative vs adjuvant-only chemotherapy for LACC have reported results recently [ 9 •, 10 , 11 ]. Neoadjuvant immunotherapy is of great interest for patients with deficient mismatch repair (dMMR) LACC given the remarkable pathologic and clinical responses reported in trials of dMMR LACC and rectal cancer [ 12 ••, 13 – 15 ].…”