Neoadjuvant Immunotherapy for Microsatellite Instability–High, Locally Advanced Colon Cancer?

In small series of patients with locally advanced microsatellite instability–high (MSI-high) colorectal cancers treated with immune checkpoint inhibitors, whether single agents or combinations, high rates of clinical and pathologic complete response have been reported. Investigators now report results of the large NICHE-2 trial, an industry-supported, phase 2 trial treating 115 patients with MSI-high colon cancer, clinical stage II or III.

Patients received one dose of ipilimumab (1 mg/kg) and two doses of nivolumab (3 mg/kg; days 1 and 15), followed by surgical resection. Thirty-seven patients had hereditary Lynch syndrome. Most patients (68%) had right-sided primary tumors; disease was clinical stage T3/4a in 21%, stage T4a/T4b in 65%, and clinical node–positive in 67%.

The primary safety endpoint of reaching timely surgery was achieved in 98% of patients; surgery was delayed in only two patients, due to therapy toxicity. All patients had R0 resection. At a median follow-up of 26.2 months, 98% of 111 eligible patients achieved a pathologic response (i.e., <50% of viable tumor cells found), 95% had a major pathologic response (<10% of viable tumor cells), and 68% had a pathologic complete response. Adjuvant chemotherapy was considered in 14 patients with residual nodal disease found at surgery but was administered to only three. Five patients had grade 3 or 4 adverse events related to immunotherapy. No recurrences were seen.