{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T17:12:33Z","timestamp":1789924353652,"version":"4.0.1"},"reference-count":31,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Mismatch repair deficiency (dMMR) or microsatellite instability (MSI) represents a distinct phenotype among solid tumors resulting in the generation of highly immunogenic neoantigens. Pembrolizumab has been approved in first-line unresectable or metastatic dMMR\/MSI colorectal cancers (CRC). We aimed to assess efficacy and tolerance of perioperative pembrolizumab in dMMR\/MSI CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>The prospective multicenter phase II trial IMHOTEP enrolled patients with localized resectable dMMR\/MSI CRC to receive one or two cycles of IV pembrolizumab 400 mg once every 6 weeks before surgery and 1-year total duration thereafter. The primary end point was pathologic complete response (pCR) rate (ypT0N0). Secondary objectives included safety, event-free survival, and overall survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      IMHOTEP enrolled 81 patients with dMMR\/MSI CRC who received at least one cycle of pembrolizumab from November 26, 2021, to February 22, 2023: median age was 66 (21-89) years, 46 (52%) were women, and 63 (71%) had clinical stage III disease at baseline. Out of the 72 patients included in the efficacy population, 38 patients (52.7% [95% CI, 41.4 to 63.9]) achieved a pCR. The exploratory post hoc analysis showed a pCR rate increased from 46% (23\/50) after one cycle to 68.2% (15\/22) after two cycles of neoadjuvant pembrolizumab (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .0125). With a median follow-up of 24.5 (95% CI, 23.3 to 25.6) months, three disease recurrences occurred. Grade \u22653 immune-related toxicities were reported in 14 (15.7%) patients including one grade 5 (myasthenia).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>The IMHOTEP trial showed promising results, with pCR achieved after one or two cycles of neoadjuvant pembrolizumab in 53% of patients with dMMR\/MSI CRC. To our knowledge, this prospective study is the first to demonstrate the feasibility and the safety of perioperative pembrolizumab.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-02169","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T19:59:08Z","timestamp":1776196748000},"page":"1520-1528","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Efficacy of Perioperative Pembrolizumab in Mismatch Repair Deficient\/Microsatellite Unstable Localized Colorectal Cancers: Results of the Phase II Trial IMHOTEP"],"prefix":"10.1200","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct04795661","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2291-5693","authenticated-orcid":true,"given":"Christelle","family":"de la Fouchardi\u00e8re","sequence":"first","affiliation":[{"name":"Medical Oncology Department, Paoli-Calmettes Institute, Aix-Marseille University, Marseille, France"},{"name":"Department of Medical Oncology, Centre L\u00e9on B\u00e9rard, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8372-5653","authenticated-orcid":true,"given":"Aziz","family":"Zaanan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Digestive Oncology, H\u00f4pital Europ\u00e9en Georges Pompidou, Paris University, Paris, France"},{"name":"Assistance Publique-H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9040-2385","authenticated-orcid":true,"given":"Aymeric","family":"de Montfort","sequence":"additional","affiliation":[{"name":"Department of Clinical Research and Innovation, Centre L\u00e9on B\u00e9rard, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sorbonne University, H\u00f4pital Saint-Antoine, AP-HP, Paris, France"},{"name":"INSERM UMRS 938, \u00c9quipe Instabilit\u00e9 des Microsatellites et Cancer, \u00c9quipe Labellis\u00e9e Par la Ligue Nationale Contre le Cancer, SIRIC CURAMUS, Centre de Recherche Saint Antoine, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9602-5162","authenticated-orcid":true,"given":"Samuel","family":"Le Sourd","sequence":"additional","affiliation":[{"name":"Medical Oncology, Centre Eug\u00e8ne Marquis, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8065-9635","authenticated-orcid":true,"given":"David","family":"Tougeron","sequence":"additional","affiliation":[{"name":"Department of Hepato-gastroenterology, Centre Hospitalo-Universitaire Poitiers, Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Soularue","sequence":"additional","affiliation":[{"name":"Department of Oncology, Institute Mutualiste Montsouris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0525-0423","authenticated-orcid":true,"given":"Olivier","family":"Dubreuil","sequence":"additional","affiliation":[{"name":"Department of Digestive Oncology, Groupe Hospitalier Diaconesses Croix Saint Simon, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7296-5464","authenticated-orcid":true,"given":"Nicolas","family":"Williet","sequence":"additional","affiliation":[{"name":"Department of Hepato-Gastroenterology and Gastrointestinal Oncology, University Institute of Cancerology and Hematology of Saint-Etienne (ICHUSE), Saint-Etienne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Samalin-Scalzi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Institut R\u00e9gional du Cancer de Montpellier (ICM), Universit\u00e9 Montpellier, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8243-8310","authenticated-orcid":true,"given":"Guillaume","family":"Piessen","sequence":"additional","affiliation":[{"name":"CNRS, Inserm, Chu Lille, UMR9020-U1277\u2014CANTHER\u2014Cancer Heterogeneity Plasticity and Resistance to Therapies, University Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2735-6448","authenticated-orcid":true,"given":"Vincent","family":"Hautefeuille","sequence":"additional","affiliation":[{"name":"Department of Hepato-Gastroenterology and Gastrointestinal Oncology, CHU d'Amiens, Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7502-7708","authenticated-orcid":true,"given":"Marine","family":"Jary","sequence":"additional","affiliation":[{"name":"Department of Digestive and Oncological Surgery, CHU Estaing, Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9105-6346","authenticated-orcid":true,"given":"Meher","family":"Ben Abdelghani","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Paul Strauss Center, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovic","family":"Evesque","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7932-0530","authenticated-orcid":true,"given":"Philippe","family":"Rochigneux","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Paoli-Calmettes Institute, Aix-Marseille University, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Blanc","sequence":"additional","affiliation":[{"name":"Department of Clinical Research and Innovation, Centre L\u00e9on B\u00e9rard, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"P\u00e9rol","sequence":"additional","affiliation":[{"name":"Department of Clinical Research and Innovation, Centre L\u00e9on B\u00e9rard, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Bibeau","sequence":"additional","affiliation":[{"name":"Department of Pathology, Besan\u00e7on University Hospital, Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8347-6957","authenticated-orcid":true,"given":"Cl\u00e9lia","family":"Coutzac","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Centre L\u00e9on B\u00e9rard, Lyon, France"},{"name":"Gastroenterology and Technologies for Health (Universit\u00e9 Claude Bernard Lyon 1, INSERM U1052, CNRS UMR5286, Centre L\u00e9on B\u00e9rard), Cancer Research Center of Lyon, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_12_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30527-1"},{"key":"e_1_3_12_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.63.4238"},{"key":"e_1_3_12_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13123063"},{"key":"e_1_3_12_5_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00046"},{"key":"e_1_3_12_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.27.1825"},{"key":"e_1_3_12_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022289"},{"key":"e_1_3_12_8_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.30.1366"},{"key":"e_1_3_12_9_2","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.12.8.17169"},{"key":"e_1_3_12_10_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.76.9901"},{"key":"e_1_3_12_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30422-9"},{"key":"e_1_3_12_12_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02105"},{"key":"e_1_3_12_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2017699"},{"key":"e_1_3_12_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)02848-4"},{"key":"e_1_3_12_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2400634"},{"key":"e_1_3_12_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03250-w"},{"key":"e_1_3_12_17_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.17_suppl.LBA3504"},{"key":"e_1_3_12_18_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.4_suppl.19"},{"key":"e_1_3_12_19_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.17_suppl.LBA1"},{"key":"e_1_3_12_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2201445"},{"key":"e_1_3_12_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2022.07.008"},{"key":"e_1_3_12_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2024.01.208"},{"key":"e_1_3_12_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy218"},{"key":"e_1_3_12_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.07.016"},{"key":"e_1_3_12_25_2","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e3181b13ca2"},{"key":"e_1_3_12_26_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21388"},{"key":"e_1_3_12_27_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01351"},{"key":"e_1_3_12_28_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.01600"},{"key":"e_1_3_12_29_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.17_suppl.LBA3512"},{"key":"e_1_3_12_30_2","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2019.1581530"},{"key":"e_1_3_12_31_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124507"},{"key":"e_1_3_12_32_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2409154"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO-25-02169","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T21:59:15Z","timestamp":1779919155000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO-25-02169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,1]]},"references-count":31,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2026,6,1]]}},"alternative-id":["10.1200\/JCO-25-02169"],"URL":"https:\/\/doi.org\/10.1200\/jco-25-02169","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,1]]},"assertion":[{"value":"2025-09-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-19","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}