Neoadjuvant chemotherapy may be viable option in locally advanced colon cancer

Although the primary endpoint of disease-free survival (DFS) was not met, results from the phase 3 NeoCol study showed that neoadjuvant chemotherapy for locally advanced colon cancer showed favourable outcomes in the number of chemotherapy cycles, postoperative complications, and downstaging.

For patients with locally advanced colon cancer, the standard-of-care is upfront surgery. Adjuvant chemotherapy is added to reduce the risk of recurrence in patients with risk factors. However, neoadjuvant chemotherapy is a widely accepted approach in numerous cancers. Potential benefits of neoadjuvant chemotherapy are the elimination of micrometastases, reduction of tumour size, prehabilitation before surgery, and reduction of adjuvant chemotherapy.

The aim of the randomised, phase 3 NeoCol trial (NCT01918527) was to assess the impact of neoadjuvant chemotherapy in locally advanced colon cancer compared with standard upfront surgery. The primary endpoint was DFS. Dr Lars Hendrik Jensen (University of Southern Denmark, Denmark) presented the preliminary results [1].

The study enrolled 250 patients with T3 (with invasive depth >5 mm) or T4 colon cancer. The participants were randomised 1:1 to upfront surgery (Arm A) or neoadjuvant chemotherapy (3 cycles CAPOX) followed by surgery (Arm B). Adjuvant chemotherapy in both arms was chosen based on the pathological stage of the cancer (minus any neoadjuvant cycles).

The primary endpoint of the study was not met: both DFS and overall survival were similar in both arms. The total number of chemotherapy cycles was trend-wise lower in Arm B compared with Arm A: 4.8 versus 5.9 (P=0.06). In Arm B, 59% of patients fulfilled the criteria for adjuvant chemotherapy compared with 73% in Arm A. Neoadjuvant chemotherapy resulted in downstaging of the tumour: 10% T2 or lower in Arm B compared with 4% in Arm A; and 59% N0 in Arm B compared with 48% in Arm A. Surgical complications were lower in Arm B, such as ileus (3% vs 8%) and anastomotic leakage (2% vs 8%). Fewer patients in Arm B had neuropathy compared with Arm A.

“Neoadjuvant chemotherapy is not superior to standard upfront surgery in locally advanced colon cancer concerning survival. However, the neoadjuvant approach may have favourable outcomes in the number of chemotherapy cycles, risk of chemotherapy toxicity, some surgical complications, and in downsizing and downstaging. Therefore, neoadjuvant chemotherapy could be offered as a viable treatment option,” concluded Dr Jensen. However, many questions remain and further analysis of the data are ongoing.

1. Jensen LH, et al. Phase III randomized clinical trial comparing the efficacy of neoadjuvant chemotherapy and standard treatment in patients with locally advanced colon cancer. Abstract LBA3503, ASCO Annual Meeting 2023, 2–6 June, Chicago, USA.

 

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Posted on 2 August, 20232 August, 2023