Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer.
Details
Serval ID
serval:BIB_6BBA7AFF15CD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer.
Journal
The New England journal of medicine
ISSN
1533-4406 (Electronic)
ISSN-L
0028-4793
Publication state
Published
Issued date
06/06/2024
Peer-reviewed
Oui
Volume
390
Number
21
Pages
1949-1958
Language
english
Notes
Publication types: Journal Article ; Clinical Trial, Phase II ; Multicenter Study
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
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.
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.
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.).
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.
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.
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.).
Keywords
Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Colonic Neoplasms/drug therapy, Colonic Neoplasms/genetics, Colonic Neoplasms/pathology, Colonic Neoplasms/surgery, Disease-Free Survival, DNA Mismatch Repair, Ipilimumab/administration & dosage, Ipilimumab/adverse effects, Ipilimumab/therapeutic use, Neoadjuvant Therapy, Nivolumab/administration & dosage, Nivolumab/adverse effects, Nivolumab/therapeutic use, Time-to-Treatment, Antineoplastic Agents, Immunological/administration & dosage, Antineoplastic Agents, Immunological/adverse effects, Antineoplastic Agents, Immunological/therapeutic use, Netherlands, Young Adult
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Web of science
Create date
14/06/2024 13:26
Last modification date
26/07/2024 6:02