{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T07:43:11Z","timestamp":1782805391203,"version":"3.54.5"},"reference-count":22,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"unspecified","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"name":"GERCOR","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,4,14]]},"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sarcopenia and growth differentiation factor 15 (GDF-15) are linked to poor cancer survival. In this exploratory analysis, we evaluated their interaction with nivolumab-ipilimumab efficacy in chemoresistant metastatic colorectal cancer (mCRC) harboring microsatellite instability and\/or mismatch-repair deficiency (MSI\/dMMR), based on the final survival analysis of the NIPICOL phase II trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>57 patients with MSI\/dMMR chemoresistant mCRC received nivolumab-ipilimumab for 3 months (3M), then, nivolumab alone for 9M. Skeletal muscle mass index (SMI) was evaluated by CT scan at baseline and 12M to assess sarcopenia. GDF-15 levels were assessed at baseline and 3M. Main endpoints were overall survival (OS) and immune Response Evaluation Criteria In Solid Tumors progression-free survival (iPFS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After excluding three patients not confirmed as MSI\/dMMR by central review, the overall median follow-up was 60.4 months. The 3-year and 5\u2009year iPFS rates were 72.0% and 65.3%, with OS rates of 77.5% and 73.3%, respectively. Among 49 patients with evaluable GDF-15, high-baseline GDF-15 was associated with poorer survival: 3-year iPFS rate of 56.3% for GDF-15\u22652500 versus 81.7% for GDF-15&lt;2500 (PFS HR=2.45, 95%\u2009CI 0.91 to 6.55), 3-year OS rates of 61.4% versus 84.5% (OS HR=2.08, 95%\u2009CI 0.70 to 6.22). Of the 48 evaluable patients for SMI, 31 (65.0%) displayed sarcopenia at baseline. 11 out of 20 (55%) patients with baseline sarcopenia and assessed for SMI at 12M, reversed sarcopenia by 12M. They had higher baseline GDF-15 levels and greater GDF-15 decrease by 3M (delta mean change: \u221269.8% vs \u221240.3%) compared with patients who remained sarcopenic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>1-year nivolumab-ipilimumab demonstrates consistent efficacy after 5-year follow-up in an MSI\/dMMR chemoresistant mCRC population. GDF-15 confirms to be a promising biomarker for sarcopenia and survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03350126\">NCT03350126<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2024-011220","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T22:00:18Z","timestamp":1747864818000},"page":"e011220","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Interplay between sarcopenia, GDF-15, and the efficacy of nivolumab plus ipilimumab in patients with mismatch repair deficient metastatic colorectal cancer: final survival analysis of the phase II GERCOR NIPICOL study"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct03350126","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04725474","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06059547","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Leonard","family":"Depotte","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Univ Paris Est Creteil, INSERM, IMRB, AP-HP, Hopital Henri Mondor, Creteil, \u00cele-de-France, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Nay","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, H\u00f4pital Saint-Antoine, Paris, \u00cele-de-France, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Borg","sequence":"additional","affiliation":[{"name":"Medical Oncology, H\u00f4pital Jean Minjoz, Besancon, France"},{"name":"TIMc, UMR 1098, Besancon, Bourgogne-Franche-Comt\u00e9, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lia","family":"Meurisse","sequence":"additional","affiliation":[{"name":"EFS, INSERM, UMR RIGHT, University of Franche-Comt\u00e9, Besancon, Bourgogne-Franche-Comt\u00e9, France"},{"name":"Methodology and Quality of Life Unit in Oncology, Besan\u00e7on University Hospital Center, Besancon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Henriques","sequence":"additional","affiliation":[{"name":"EFS, INSERM, UMR RIGHT, University of Franche-Comt\u00e9, Besancon, Bourgogne-Franche-Comt\u00e9, France"},{"name":"Methodology and Quality of Life Unit in Oncology, Besan\u00e7on University Hospital Center, Besancon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaafar","family":"Bennouna","sequence":"additional","affiliation":[{"name":"Department of Digestive Oncology, University Hospital Centre Nantes, Nantes, Pays de la Loire, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"De La Fouchardi\u00e8re","sequence":"additional","affiliation":[{"name":"Medical Oncology, Centre Leon Berard, Lyon, Rh\u00f4ne-Alpes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8065-9635","authenticated-orcid":false,"given":"David","family":"Tougeron","sequence":"additional","affiliation":[{"name":"Department of Hepato-Gastroenterology, CHU Poitiers, Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibault","family":"Mazard","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Institut de Recherche en Canc\u00e9rologie de Montpellier, Montpellier, Languedoc-Roussillon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoist","family":"Chibaudel","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Franco-Britannique, Fondation Cognacq-Jay, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Tournigand","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Univ Paris Est Creteil, INSERM, IMRB, AP-HP, Hopital Henri Mondor, Creteil, \u00cele-de-France, France"},{"name":"GERCOR, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dewi","family":"Vernerey","sequence":"additional","affiliation":[{"name":"EFS, INSERM, UMR RIGHT, University of Franche-Comt\u00e9, Besancon, Bourgogne-Franche-Comt\u00e9, France"},{"name":"Methodology and Quality of Life Unit in Oncology, Besan\u00e7on University Hospital Center, Besancon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Pigneur","sequence":"additional","affiliation":[{"name":"Department of Radiology, University Hospital of Henri Mondor, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5103-7095","authenticated-orcid":false,"given":"Thierry","family":"Andre","sequence":"additional","affiliation":[{"name":"GERCOR, Paris, France"},{"name":"Department of Medical Oncology, H\u00f4pital Saint-Antoine, AP-HP, and 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, Sorbonne Universite, Paris, \u00cele-de-France, 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