Efficacy of neoadjuvant nivolumab/relatlimab in locally advanced colon cancer

A neoadjuvant immunotherapy regimen with nivolumab/relatlimab in locally advanced mismatch repair deficient (dMMR) colon cancer induces high rates of pathologic responses, as shown by data of the NICHE-3 trial recently published on Nature Medicine.

Patients with dMMR colon cancer have limited benefit from chemotherapy but these tumors have been shown to respond exceptionally well to neoadjuvant anti-PD-1 plus anti-CTLA-4, with high rates of pathologic responses; authors thus investigated the efficacy and toxicity of anti-PD-1 plus anti-LAG-3, based on positive data obtained in melanoma patients. In the NICHE-3 trial, 59 patients with locally advanced dMMR colon cancer were treated with two 4-weekly cycles of nivolumab (480 mg) plus relatlimab (480 mg) before surgery. Pathologic response was observed in 97% of patients with 68% pathologic complete responses and an acceptable safety profile; at a median follow-up of 8 months, only one patient had a recurrence of disease. As authors explain, «At present, pathologic response after neoadjuvant treatment is not yet an accepted surrogate endpoint for colon cancer, unlike the situation in other tumor types, such as triple-negative breast cancer. If an association between pathologic response and disease-free survival is confirmed, this surrogate endpoint would allow more rapid evaluation of neo-adjuvant immunotherapy studies in dMMR colon cancer and, thereby, accelerate advances in treatments. Taken together, these and previous data suggest that patients with locally advanced dMMR colon cancer treated with a short course of neoadjuvant immune checkpoint blockade have a lower risk of recurrence compared to studies treating this patient population with (neo)adjuvant chemotherapy. Based on the pathologic response data observed, randomized studies comparing neoadjuvant immunotherapy regimens to adjuvant chemotherapy may be considered unethical», authors conclude.