KEY TAKEAWAYS
- The NICHE-2 phase 3 trial evaluated the safety and efficacy of neoadjuvant immunotherapy in patients with non-metastatic dMMR colon cancer.
- The primary aim of the study was to evaluate the safety and 3-year (DFS) in the (ITT) population and the (PP) population, respectively.
- Patients received one dose of ipilimumab and two doses of nivolumab and underwent surgery within 6 weeks of registration.
- The study demonstrated a 95% central pathologic response rate, including a 67% complete response rate, and no disease recurrence at a median follow-up of 13 months.
- Grade 3-4 immune-related adverse events were observed in 3% of patients, and only 3 patients experienced a delay in surgery, meeting the safety primary endpoint.
- The study suggests that neoadjuvant immunotherapy may become a standard of care for dMMR colon cancer.
Several types of cancer have responded favorably to neoadjuvant immunotherapy. In NICHE, the first neoadjuvant immunotherapy study for CC, all dMMR tumors showed pathologic responses. Despite adjuvant chemotherapy, three-year recurrence risks of over 40% in high-risk (T4 and/or N2) stage III tumors are concerning. Still, disease-free survival (DFS) in patients (pts) with stage III dMMR CC is similar to that of pMMR pts. There is an immediate need to boost health outcomes for these patients.
Patients in the NICHE-2 study were given one dose of ipilimumab (1mg/kg) and two doses of nivolumab (3mg/kg) before undergoing surgery within 6 weeks of registration if they had non-metastatic dMMR CC. Primary endpoints included both 1-year and 3-year DFS and ITT for safety (PP). Completeness of treatment and major pathologic response were secondary endpoints. For pathologic response, 50% RVT was considered successful, while for MPR, 10% RVT was considered successful. We report here on pathologic responses and other measures of safety.
There were 112 pts in total. The primary endpoint of safety was achieved, with only three patients experiencing surgical delays due to immune-related adverse events in grades 3-4. Baseline radiologic evaluation of the PP population (n=107) revealed that 89% of the tumors were stage III, 77% were high-risk stage III (Table), and 64% were T4. Pathologic response was seen in 106/107 (99%) pts, including 102/107 (95%) MPR and 4 (4%) PR, with a median time from the first dose to surgery of 5 weeks. Seventy-two of 107 patients (67%). There was no disease recurrence in any patient at a median follow-up of 13 months (range, 1-57).
Pathologic responses to short-term neoadjuvant nivolumab plus ipilimumab in a large cohort of dMMR CC pts were previously reported, with an MPR rate of 95%, including 67% pCR. These results were confirmed in NICHE-2. The preliminary data on survival rates indicate that neoadjuvant immunotherapy has a good chance of becoming the gold standard of care, opening the door to further investigation of organ-sparing methods.
Source:https://oncologypro.esmo.org/meeting-resources/esmo-congress/neoadjuvant-immune-checkpoint-inhibition-in-locally-advanced-mmr-deficient-colon-cancer-the-niche-2-study
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03026140\
Chalabi M., VerschoorY.L., Berg J. van den, Sikorska. K, Beets G., Lent A.V., M.C. Grootscholten, A. Aalbers, N. Buller, H. Marsman, E. Hendriks, P.W.A. Burger, T. Aukema, S. Oosterling, R. Beets-Tan, T.N. Schumacher, M. van Leerdam, E.E. Voest, J.B.A.G. HaanenLBA7 – Neoadjuvant immune checkpoint inhibition in locally advanced MMR-deficient colon cancer: The NICHE-2 study- Annals of Oncology (2022) 33 (suppl_7): S808-S869. 10.1016/annonc/annonc1089| OncologyPRO. (n.d.). Oncologypro.esmo.org. https://oncologypro.esmo.org/meeting-resources/esmo-congress/neoadjuvant-immune-checkpoint-inhibition-in-locally-advanced-mmr-deficient-colon-cancer-the-niche-2-study
