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
Background 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 mi...
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BMJ Publishing Group
2025-05-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/5/e011220.full |
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| author | Christelle de La Fouchardière Jaafar Bennouna David Tougeron Thierry André Christophe Tournigand Christophe Borg Romain Cohen Thibault Mazard Dewi Vernerey Frédéric Pigneur Julie Henriques Aurélia Meurisse Benoist Chibaudel Leonard Depotte Paula Nay |
| author_facet | Christelle de La Fouchardière Jaafar Bennouna David Tougeron Thierry André Christophe Tournigand Christophe Borg Romain Cohen Thibault Mazard Dewi Vernerey Frédéric Pigneur Julie Henriques Aurélia Meurisse Benoist Chibaudel Leonard Depotte Paula Nay |
| author_sort | Christelle de La Fouchardière |
| collection | DOAJ |
| description | Background 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.Patients and methods 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).Results 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 year 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≥2500 versus 81.7% for GDF-15<2500 (PFS HR=2.45, 95% CI 0.91 to 6.55), 3-year OS rates of 61.4% versus 84.5% (OS HR=2.08, 95% CI 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: −69.8% vs −40.3%) compared with patients who remained sarcopenic.Conclusion 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.Trial registration number NCT03350126. |
| format | Article |
| id | doaj-art-25eeb6d82e9549a293f552f76d2e830e |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-05-01 |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-25eeb6d82e9549a293f552f76d2e830e2025-08-20T02:32:38ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-05-0113510.1136/jitc-2024-011220Interplay 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 studyChristelle de La Fouchardière0Jaafar Bennouna1David Tougeron2Thierry André3Christophe Tournigand4Christophe Borg5Romain Cohen6Thibault Mazard7Dewi Vernerey8Frédéric Pigneur9Julie Henriques10Aurélia Meurisse11Benoist Chibaudel12Leonard Depotte13Paula Nay148 Medical Oncology, Centre Leon Berard, Lyon, Rhône-Alpes, France7 Department of Digestive Oncology, University Hospital Centre Nantes, Nantes, Pays de la Loire, France9 Department of Hepato-Gastroenterology, CHU Poitiers, Poitiers, France12 GERCOR, Paris, France1 Department of Medical Oncology, Univ Paris Est Creteil, INSERM, IMRB, AP-HP, Hopital Henri Mondor, Creteil, Île-de-France, France3 Medical Oncology, Hôpital Jean Minjoz, Besancon, France14 Department of Medical Oncology, Hôpital Saint-Antoine, AP-HP, and INSERM UMRS 938, Équipe Instabilité des Microsatellites et Cancer, Équipe Labellisée par la Ligue Nationale Contre le Cancer, SIRIC CURAMUS, Centre de recherche Saint Antoine, Sorbonne Universite, Paris, Île-de-France, France10 Department of Medical Oncology, Institut de Recherche en Cancérologie de Montpellier, Montpellier, Languedoc-Roussillon, France5 EFS, INSERM, UMR RIGHT, University of Franche-Comté, Besancon, Bourgogne-Franche-Comté, France13 Department of Radiology, University Hospital of Henri Mondor, Créteil, France5 EFS, INSERM, UMR RIGHT, University of Franche-Comté, Besancon, Bourgogne-Franche-Comté, France5 EFS, INSERM, UMR RIGHT, University of Franche-Comté, Besancon, Bourgogne-Franche-Comté, France11 Department of Medical Oncology, Hospital Franco-Britannique, Fondation Cognacq-Jay, Paris, France1 Department of Medical Oncology, Univ Paris Est Creteil, INSERM, IMRB, AP-HP, Hopital Henri Mondor, Creteil, Île-de-France, France2 Department of Medical Oncology, Hôpital Saint-Antoine, Paris, Île-de-France, FranceBackground 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.Patients and methods 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).Results 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 year 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≥2500 versus 81.7% for GDF-15<2500 (PFS HR=2.45, 95% CI 0.91 to 6.55), 3-year OS rates of 61.4% versus 84.5% (OS HR=2.08, 95% CI 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: −69.8% vs −40.3%) compared with patients who remained sarcopenic.Conclusion 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.Trial registration number NCT03350126.https://jitc.bmj.com/content/13/5/e011220.full |
| spellingShingle | Christelle de La Fouchardière Jaafar Bennouna David Tougeron Thierry André Christophe Tournigand Christophe Borg Romain Cohen Thibault Mazard Dewi Vernerey Frédéric Pigneur Julie Henriques Aurélia Meurisse Benoist Chibaudel Leonard Depotte Paula Nay 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 Journal for ImmunoTherapy of Cancer |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://jitc.bmj.com/content/13/5/e011220.full |
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