Neoadjuvant nivolumab plus ipilimumab could be a new standard of care for patients with mismatch repair-deficient (dMMR) colon cancer, according to a presentation at ESMO Congress 2022.

The combination was well tolerated and produced an “unprecedented” major pathologic response rate in the NICHE-2 study, according to study presenter Myriam Chalabi, MD, PhD, of the Netherlands Cancer Institute in Amsterdam.

NICHE-2 enrolled patients with previously untreated, nonmetastatic, dMMR colon cancer. Patients received 1 dose of ipilimumab at 1 mg/kg and 2 doses of nivolumab at 3 mg/kg each. After immunotherapy, patients proceeded to surgery, ideally within 6 weeks of study registration.

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There were 112 patients in the intent-to-treat population. At baseline, the median age was 60 (range, 20-82) years, 74% of patients had radiologic high-risk stage III disease, and 48% had radiologic high-risk status with both T4 and N2 features. 

The co-primary endpoints of this study are safety/feasibility and disease-free survival (DFS). The researchers specified that the safety/feasibility endpoint would be met if 95% of patients underwent surgery on time (with a delay of no more than 2 weeks). 

As 98% of patients underwent surgery on time, the safety/feasibility endpoint was met. Ultimately, all patients underwent surgery, and all had R0 resections. The median time from the first dose of treatment to surgery was 5.4 weeks.

In the per-protocol population (n=107), 95% of patients achieved a major pathologic response, 67% had a pathologic complete response, and 4% had a partial response. 

At a median follow-up of 13.1 months, there have been no disease recurrences. The 3-year DFS results are expected in 2023, Dr Chalabi noted. 

In the intent-to-treat population (n=112), 61% of patients had immune-related adverse events (AEs), and 4% had grade 3 or higher immune-related AEs. Two percent of patients had AEs that led to the delay of surgery. 

Any surgery-related AEs occurred in 21% of patients, and 13% of patients had grade 3 or higher surgery-related AEs.   

Based on these results, Dr Chalabi concluded that neoadjuvant immunotherapy has the potential to become standard care for dMMR colon cancer.

Disclosures: This research was supported by Bristol Myers Squibb. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of disclosures.

ReferenceChalabi M, Verschoor YL, van den Berg J, et al. Neoadjuvant immune checkpoint inhibition in locally advanced MMR-deficient colon cancer: The NICHE-2 study. Presented at ESMO 2022; September 9-13, 2022. Abstract LBA7.