Neoadjuvant immunotherapy in advanced colon cancer

A new paper published on The New England Journal of Medicine shows that a neoadjuvant immunotherapy with nivolumab plus ipilimumab has an acceptable safety and can lead to a pathological response in a high proportion of patients with mismatch repair-deficient (dMMR) locally advanced colon cancer.

This phase 2 study enrolled 115 patients with with non-metastatic, locally advanced, previously untreated dMMR colon cancer. In these patients the efficacy of chemotherapy is limited; participants were treated with neoadjuvant immunotherapy with nivolumab plus ipilimumab, then underwent surgery. Grade 3 or 4 immune-related adverse events occurred in 4% of the patients and none discontinued treatment because of adverse events; 98% of patients had a pathological response, including 95% with a major pathological response and 68% with pathological complete response. With a median follow-up of 26 months, no patients have had recurrence of disease. «We observed a major pathological response and a pathological complete response in high proportions of patients regardless of tumor staging», authors say. «Despite the high percentage of high-risk tumors and the omission of chemotherapy in most patients in our study, no patient has had disease recurrence to date. The high proportion of patients with a pathological response observed after only 4 weeks of treatment in our study, together with the safety profile, may provide sufficient justification to provide immunotherapy to patients with radiographically assessed high-risk disease. With the high incidence of disease recurrence in patients with dMMR tumors that are stage T4, have spread to the lymph nodes, or both, despite adjuvant chemotherapy, improved systemic treatment is needed», authors conclude.