KEY TAKEAWAYS
- The NICHE phase 2 trial aimed to investigate the efficacy of neoadjuvant immunotherapy in patients with locally advanced dMMR colon cancer.
- The study aimed to determine DFS and OS.
- Researchers observed a favorable safety profile and substantial pathological response with neoadjuvant nivolumab + ipilimumab.
Mismatch repair-deficient (dMMR) tumors can be found in 10 to 15% of patients with nonmetastatic colon cancer, where chemotherapy efficacy is often restricted. Neoadjuvant immunotherapy presents a promising avenue, yet comprehensive data remains scarce.
Myriam Chalabi and the team aimed to assess the efficacy and safety of neoadjuvant immunotherapy in patients with locally advanced dMMR colon cancer.
They performed an inclusive analysis of a phase 2 study involving patients with nonmetastatic, locally advanced, previously untreated dMMR colon cancer. Patients received neoadjuvant nivolumab plus ipilimumab. The study assessed safety, defined by timely surgery (≤2-week delay of planned surgery due to treatment-related toxic events) and 3-year disease-free survival (DFS) as primary endpoints. Secondary endpoints included pathological response and results of genomic analyses.
About 115 enrolled patients, 113 (98%; 97.5% [CI], 93 to 100) underwent timely surgery; 2 patients experienced surgery delayed by more than 2 weeks. Grade 3 or 4 immune-related adverse events occurred in 5 patients (4%), with no treatment discontinuations due to adverse events (AE’s).
Among 111 patients included in the efficacy analysis, a pathological response was observed in 109 (98%; 95% CI, 94 to 100), including 105 (95%) with a major pathological response (≤10% residual viable tumor) and 75 (68%) with a pathological complete response (0% residual viable tumor). With a median follow-up of 26 months (range, 9 to 65), no patients have had a recurrence of disease.
The study concluded that neoadjuvant nivolumab plus ipilimumab demonstrated an acceptable safety profile and elicited a substantial pathological response in a significant proportion of patients with locally advanced dMMR colon cancer. (Funded by Bristol Myers Squibb; NICHE-2).
The trial was sponsored by the Netherlands Cancer Institute.
Source: https://pubmed.ncbi.nlm.nih.gov/38838311/
Clinical Trial: https://clinicaltrials.gov/study/NCT03026140
Chalabi M, Verschoor YL, Tan PB, et al. (2024). “Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer.” N Engl J Med. 2024 Jun 6;390(21):1949-1958. doi: 10.1056/NEJMoa2400634. PMID: 38838311.
