TY - JOUR
T1 - Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer
AU - Chalabi, Myriam
AU - Verschoor, Yara L.
AU - Tan, Pedro Batista
AU - Balduzzi, Sara
AU - Van Lent, Anja U.
AU - Grootscholten, Cecile
AU - Dokter, Simone
AU - Büller, Nikè V.
AU - Grotenhuis, Brechtje A.
AU - Kuhlmann, Koert
AU - Burger, Jacobus W.
AU - Huibregtse, Inge L.
AU - Aukema, Tjeerd S.
AU - Hendriks, Eduard R.
AU - Oosterling, Steven J.
AU - Snaebjornsson, Petur
AU - Voest, Emile E.
AU - Wessels, Lodewyk F.
AU - Beets-Tan, Regina G.
AU - Van Leerdam, Monique E.
AU - Schumacher, Ton N.
AU - van den Berg, José G.
AU - Beets, Geerard L.
AU - Haanen, John B.
N1 - Publisher Copyright:
Copyright © 2024 Massachusetts Medical Society.
PY - 2024/6/6
Y1 - 2024/6/6
N2 - BACKGROUND: Mismatch repair-deficient (dMMR) tumors can be found in 10 to 15% of patients with nonmetastatic colon cancer. In these patients, the efficacy of chemotherapy is limited. The use of neoadjuvant immunotherapy has shown promising results, but data from studies of this approach are limited. METHODS: We conducted a phase 2 study in which patients with nonmetastatic, locally advanced, previously untreated dMMR colon cancer were treated with neoadjuvant nivolumab plus ipilimumab. The two primary end points were safety, defined by timely surgery (i.e., =2-week delay of planned surgery owing to treatment-related toxic events), and 3-year disease-free survival. Secondary end points included pathological response and results of genomic analyses. RESULTS: Of 115 enrolled patients, 113 (98%; 97.5% confidence interval [CI], 93 to 100) underwent timely surgery; 2 patients had surgery delayed by more than 2 weeks. Grade 3 or 4 immune-related adverse events occurred in 5 patients (4%), and none of the patients discontinued treatment because of adverse events. Among the 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 (defined as =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 recurrence of disease. CONCLUSIONS: In patients with locally advanced dMMR colon cancer, neoadjuvant nivolumab plus ipilimumab had an acceptable safety profile and led to a pathological response in a high proportion of patients. (Funded by Bristol Myers Squibb; NICHE-2 ClinicalTrials.gov number, NCT03026140.).
AB - BACKGROUND: Mismatch repair-deficient (dMMR) tumors can be found in 10 to 15% of patients with nonmetastatic colon cancer. In these patients, the efficacy of chemotherapy is limited. The use of neoadjuvant immunotherapy has shown promising results, but data from studies of this approach are limited. METHODS: We conducted a phase 2 study in which patients with nonmetastatic, locally advanced, previously untreated dMMR colon cancer were treated with neoadjuvant nivolumab plus ipilimumab. The two primary end points were safety, defined by timely surgery (i.e., =2-week delay of planned surgery owing to treatment-related toxic events), and 3-year disease-free survival. Secondary end points included pathological response and results of genomic analyses. RESULTS: Of 115 enrolled patients, 113 (98%; 97.5% confidence interval [CI], 93 to 100) underwent timely surgery; 2 patients had surgery delayed by more than 2 weeks. Grade 3 or 4 immune-related adverse events occurred in 5 patients (4%), and none of the patients discontinued treatment because of adverse events. Among the 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 (defined as =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 recurrence of disease. CONCLUSIONS: In patients with locally advanced dMMR colon cancer, neoadjuvant nivolumab plus ipilimumab had an acceptable safety profile and led to a pathological response in a high proportion of patients. (Funded by Bristol Myers Squibb; NICHE-2 ClinicalTrials.gov number, NCT03026140.).
U2 - 10.1056/NEJMoa2400634
DO - 10.1056/NEJMoa2400634
M3 - Article
SN - 0028-4793
VL - 390
SP - 1949
EP - 1958
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 21
ER -