{"entity":{"id":"paper-niche-2-nat-med-2020","kind":"paper","name":"Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers","aka":[],"tldr":"Published report from the NICHE-2 trial registered as NCT03026140, in Nature Medicine (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"PD-1 plus CTLA-4 blockade is highly effective in advanced-stage, mismatch repair (MMR)-deficient (dMMR) colorectal cancers, yet not in MMR-proficient (pMMR) tumors. We postulated a higher efficacy of neoadjuvant immunotherapy in early-stage colon cancers. In the exploratory NICHE study (ClinicalTrials.gov: NCT03026140), patients with dMMR or pMMR tumors received a single dose of ipilimumab and two doses of nivolumab before surgery, the pMMR group with or without celecoxib. The primary objective was safety and feasibility; 40 patients with 21 dMMR and 20 pMMR tumors were treated, and 3 patients received nivolumab monotherapy in the safety run-in. Treatment was well tolerated and all patients underwent radical resections without delays, meeting the primary endpoint. Of the patients who received ipilimumab + nivolumab (20 dMMR and 15 pMMR tumors), 35 were evaluable for efficacy and translational endpoints. Pathological response was observed in 20/20 (100%; 95% exact confidence interval (CI): 86-100%) dMMR tumors, with 19 major pathological responses (MPRs, ≤10% residual viable tumor) and 12 pathological complete responses. In pMMR tumors, 4/15 (27%; 95% exact CI: 8-55%) showed pathological responses, with 3 MPRs and 1 partial response. CD8 + PD-1 + T cell infiltration was predictive of response in pMMR tumors. These data indicate that neoadjuvant immunotherapy may have the potential to become the standard of care for a defined group of colon cancer patients when validated in larger studies with at least 3 years of disease-free survival data.\n\nIndexed on Europe PMC as PubMed record 32251400 (DOI 10.1038/s41591-020-0805-8). Its abstract cites the registry id NCT03026140, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2020","url":"https://doi.org/10.1038/s41591-020-0805-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32251400/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32251400"},{"label":"ClinicalTrials.gov NCT03026140","url":"https://clinicaltrials.gov/study/NCT03026140"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["niche-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2020,"doi":"10.1038/s41591-020-0805-8","pmid":"32251400","authors":"Chalabi M, Fanchi LF, Dijkstra KK, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03026140 with the most citations, so it is the natural first reading for anyone following the NICHE-2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-niche-2-nat-med-2020/","neighbours":{"trial":[{"id":"niche-2","kind":"trial","name":"NICHE-2","route":"/trials/niche-2/"}],"journal":[{"id":"nature-medicine","kind":"journal","name":"Nature Medicine","route":"/journals/nature-medicine/"}]}}