RECIST and iRECIST criteria for the evaluation of nivolumab plus ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the GERCOR NIPICOL phase II study
Background Immune checkpoint inhibitors (ICIs) are highly effective in patients with microsatellite instability/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC). Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria may underestimate response to ICIs due to the p...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2020-07-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e001499.full |
| _version_ | 1797260203951915008 |
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| author | Christelle de La Fouchardière Jaafar Bennouna David Tougeron Magali Svrcek Thierry André Christophe Tournigand Christophe Borg Romain Cohen Marie-Line Garcia-Larnicol Thibault Mazard Yves Menu Dewi Vernerey Aurélia Meurisse Benoist Chibaudel |
| author_facet | Christelle de La Fouchardière Jaafar Bennouna David Tougeron Magali Svrcek Thierry André Christophe Tournigand Christophe Borg Romain Cohen Marie-Line Garcia-Larnicol Thibault Mazard Yves Menu Dewi Vernerey Aurélia Meurisse Benoist Chibaudel |
| author_sort | Christelle de La Fouchardière |
| collection | DOAJ |
| description | Background Immune checkpoint inhibitors (ICIs) are highly effective in patients with microsatellite instability/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC). Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria may underestimate response to ICIs due to the pseudoprogression phenomenon. The GERCOR NIPICOL phase II study aimed to evaluate the frequency of pseudoprogressions in patients with MSI/dMMR mCRC treated with nivolumab and ipilimumab.Methods Patients with MSI/dMMR mCRC previously treated with fluoropyrimidines, oxaliplatin, and irinotecan with/without targeted therapies received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four cycles then nivolumab 3 mg/kg every 2 weeks until progression or a maximum of 20 cycles. Computed tomography scan tumor assessments were done every 6 weeks for 24 weeks and then every 12 weeks. The primary endpoint was disease control rate at 12 weeks according to RECIST 1.1 and iRECIST by central review.Results Of 57 patients included between December 2017 and November 2018, 48.0% received ≥3 prior lines of chemotherapy, 18.0% had BRAFV600E mutation, and 56.0% had Lynch syndrome-related cancer. Seven patients (12.0%) discontinued treatment due to adverse events; one died due to a treatment-related adverse event. The disease control rate (DCR) at 12 weeks was 86.0% with RECIST 1.1% and 87.7% with iRECIST. Two pseudoprogressions (3.5%) were observed, at week 6 and at week 36, representing 18% of patients with disease progression per RECIST 1.1 criteria. With a median follow-up of 18.4 months, median progression-free survival (PFS) and overall survival (OS) were not reached. The 12-month PFS rate was 72.9% with RECIST 1.1% and 76.5% with iRECIST. The 12-month OS rate was 84%. Overall response rate was 59.7% with both criteria. RAS/BRAF status, sidedness, Lynch syndrome, and other baseline parameters were not associated with PFS.Conclusion Pseudoprogression is rare in patients with MSI/dMMR mCRC treated with nivolumab and ipilimumab. This combined ICI therapy confirms impressive DCR and survival outcomes in these patients.Trial registration number NCT03350126. |
| first_indexed | 2024-04-24T23:21:36Z |
| format | Article |
| id | doaj.art-51c42fd68b8549f1b23166f45ed68555 |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-04-24T23:21:36Z |
| publishDate | 2020-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-51c42fd68b8549f1b23166f45ed685552024-03-16T07:05:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-07-018210.1136/jitc-2020-001499RECIST and iRECIST criteria for the evaluation of nivolumab plus ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the GERCOR NIPICOL phase II studyChristelle de La Fouchardière0Jaafar Bennouna1David Tougeron2Magali Svrcek3Thierry André4Christophe Tournigand5Christophe Borg6Romain Cohen7Marie-Line Garcia-Larnicol8Thibault Mazard9Yves Menu10Dewi Vernerey11Aurélia Meurisse12Benoist Chibaudel135 Department of Medical Oncology, Centre Léon Bérard, Lyon, FranceDepartment of Pneumology, Thoracic Oncology, University Hospital Centre Nantes, Nantes, France6 Department of Gastroenterology, Poitiers University Hospital and University of Poitiers, Poitiers, FranceSorbonne Université, Department of Pathology, Hôpital Saint-Antoine, AP-HP, and INSERM, Unité Mixte de Recherche Scientifique 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, FranceDepartment of Medical Oncology, Saint-Antoine Hospital, APHP, Sorbonne University, Paris, FranceAff8 grid.412116.10000000122921474Hôpital Henri Mondor Créteil France7 Department of Medical Oncology, University Hospital of Besançon, Besançon, FranceDepartment of Medical Oncology, Saint-Antoine Hospital, APHP, Sorbonne University, Paris, France2 GERCOR, Paris, France1 Department of Digestive Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USASorbonne Université and Hospital Saint Antoine, Department of Medical rodiology, AP-HP, Paris, FranceUniversité Franche-Comté, INSERM, EFS BFC, UMR1098 RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France3 Department of Oncology, Besançon University Hospital, Methodology and Quality of Life Unit, Besançon, France9 Department of Medical Oncology, Franco-British Hospital, Fondation Cognacq-Jay, Levallois-Perret, FranceBackground Immune checkpoint inhibitors (ICIs) are highly effective in patients with microsatellite instability/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC). Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria may underestimate response to ICIs due to the pseudoprogression phenomenon. The GERCOR NIPICOL phase II study aimed to evaluate the frequency of pseudoprogressions in patients with MSI/dMMR mCRC treated with nivolumab and ipilimumab.Methods Patients with MSI/dMMR mCRC previously treated with fluoropyrimidines, oxaliplatin, and irinotecan with/without targeted therapies received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four cycles then nivolumab 3 mg/kg every 2 weeks until progression or a maximum of 20 cycles. Computed tomography scan tumor assessments were done every 6 weeks for 24 weeks and then every 12 weeks. The primary endpoint was disease control rate at 12 weeks according to RECIST 1.1 and iRECIST by central review.Results Of 57 patients included between December 2017 and November 2018, 48.0% received ≥3 prior lines of chemotherapy, 18.0% had BRAFV600E mutation, and 56.0% had Lynch syndrome-related cancer. Seven patients (12.0%) discontinued treatment due to adverse events; one died due to a treatment-related adverse event. The disease control rate (DCR) at 12 weeks was 86.0% with RECIST 1.1% and 87.7% with iRECIST. Two pseudoprogressions (3.5%) were observed, at week 6 and at week 36, representing 18% of patients with disease progression per RECIST 1.1 criteria. With a median follow-up of 18.4 months, median progression-free survival (PFS) and overall survival (OS) were not reached. The 12-month PFS rate was 72.9% with RECIST 1.1% and 76.5% with iRECIST. The 12-month OS rate was 84%. Overall response rate was 59.7% with both criteria. RAS/BRAF status, sidedness, Lynch syndrome, and other baseline parameters were not associated with PFS.Conclusion Pseudoprogression is rare in patients with MSI/dMMR mCRC treated with nivolumab and ipilimumab. This combined ICI therapy confirms impressive DCR and survival outcomes in these patients.Trial registration number NCT03350126.https://jitc.bmj.com/content/8/2/e001499.full |
| spellingShingle | Christelle de La Fouchardière Jaafar Bennouna David Tougeron Magali Svrcek Thierry André Christophe Tournigand Christophe Borg Romain Cohen Marie-Line Garcia-Larnicol Thibault Mazard Yves Menu Dewi Vernerey Aurélia Meurisse Benoist Chibaudel RECIST and iRECIST criteria for the evaluation of nivolumab plus ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the GERCOR NIPICOL phase II study Journal for ImmunoTherapy of Cancer |
| title | RECIST and iRECIST criteria for the evaluation of nivolumab plus ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the GERCOR NIPICOL phase II study |
| title_full | RECIST and iRECIST criteria for the evaluation of nivolumab plus ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the GERCOR NIPICOL phase II study |
| title_fullStr | RECIST and iRECIST criteria for the evaluation of nivolumab plus ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the GERCOR NIPICOL phase II study |
| title_full_unstemmed | RECIST and iRECIST criteria for the evaluation of nivolumab plus ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the GERCOR NIPICOL phase II study |
| title_short | RECIST and iRECIST criteria for the evaluation of nivolumab plus ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the GERCOR NIPICOL phase II study |
| title_sort | recist and irecist criteria for the evaluation of nivolumab plus ipilimumab in patients with microsatellite instability high mismatch repair deficient metastatic colorectal cancer the gercor nipicol phase ii study |
| url | https://jitc.bmj.com/content/8/2/e001499.full |
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