Association of a gene-expression subtype to outcome and treatment response in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab
Background Immune checkpoint inhibitors have been approved and currently used in the clinical management of recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. The reported benefit in clinical trials is variable and heterogeneous. Our study aims at exploring and comp...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2024-01-01
|
| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/1/e007823.full |
| _version_ | 1827360202967482368 |
|---|---|
| author | Nerina Denaro Lisa Licitra Marco Merlano Francesco Perri Paolo Bossi Cristina Gurizzan Federica Perrone Athanassios Argiris Loris De Cecco Stefano Cavalieri Mara Serena Serafini Federico Pistore Deborah Lenoci Silvana Canevari Mario Airoldi Maria Cossu Rocca Primoz Strojan Cvetka Grasic Kuhar Andrea Vingiani Maria Grazia Ghi Alessandra Cassano Giacomo Allegrini |
| author_facet | Nerina Denaro Lisa Licitra Marco Merlano Francesco Perri Paolo Bossi Cristina Gurizzan Federica Perrone Athanassios Argiris Loris De Cecco Stefano Cavalieri Mara Serena Serafini Federico Pistore Deborah Lenoci Silvana Canevari Mario Airoldi Maria Cossu Rocca Primoz Strojan Cvetka Grasic Kuhar Andrea Vingiani Maria Grazia Ghi Alessandra Cassano Giacomo Allegrini |
| author_sort | Nerina Denaro |
| collection | DOAJ |
| description | Background Immune checkpoint inhibitors have been approved and currently used in the clinical management of recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. The reported benefit in clinical trials is variable and heterogeneous. Our study aims at exploring and comparing the predictive role of gene-expression signatures with classical biomarkers for immunotherapy-treated R/M HNSCC patients in a multicentric phase IIIb trial.Methods Clinical data were prospectively collected in Nivactor tiral (single-arm, open-label, multicenter, phase IIIb clinical trial in platinum-refractory HNSCC treated with nivolumab). Findings were validated in an external independent cohort of immune-treated HNSCC patients, divided in long-term and short-term survivors (overall survival >18 and <6 months since the start of immunotherapy, respectively). Pretreatment tumor tissue specimen from immunotherapy-treated R/M HNSCC patients was used for PD-L1 (Tumor Proportion Score; Combined Positive Score (CPS)) and Tumor Mutational Burden (Oncopanel TSO500) evaluation and gene expression profiling; classical biomarkers and immune signatures (retrieved from literature) were challenged in the NIVACTOR dataset.Results Cluster-6 (Cl6) stratification of NIVACTOR cases in high score (n=16, 20%) and low score (n=64, 80%) demonstrated a statistically significant and clinically meaningful improvement in overall survival in the high-score cases (p=0.00028; HR=4.34, 95% CI 1.84 to 10.22) and discriminative ability reached area under the curve (AUC)=0.785 (95% CI 0.603 to 0.967). The association of high-score Cl6 with better outcome was also confirmed in: (1) NIVACTOR progression-free survival (p=4.93E-05; HR=3.71, 95% CI 1.92 to 7.18) and objective-response-rate (AUC=0.785; 95% CI 0.603 to 0.967); (2) long survivors versus short survivors (p=0.00544). In multivariate Cox regression analysis, Cl6 was independent from Eastern Cooperative Oncology Group performance status, PDL1-CPS, and primary tumor site.Conclusions These data highlight the presence of underlying biological differences able to predict survival and response following treatment with immunotherapy in platinum-refractory R/M HNSCC that could have translational implications improving treatment selection.Trial registration number EudraCT Number: 2017-000562-30. |
| first_indexed | 2024-03-08T06:43:36Z |
| format | Article |
| id | doaj.art-b9740be0719d4304a7e872232992bfd0 |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-03-08T06:43:36Z |
| publishDate | 2024-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-b9740be0719d4304a7e872232992bfd02024-02-03T08:20:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-01-0112110.1136/jitc-2023-007823Association of a gene-expression subtype to outcome and treatment response in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumabNerina Denaro0Lisa Licitra1Marco Merlano2Francesco Perri3Paolo Bossi4Cristina Gurizzan5Federica Perrone6Athanassios Argiris7Loris De Cecco8Stefano Cavalieri9Mara Serena Serafini10Federico Pistore11Deborah Lenoci12Silvana Canevari13Mario Airoldi14Maria Cossu Rocca15Primoz Strojan16Cvetka Grasic Kuhar17Andrea Vingiani18Maria Grazia Ghi19Alessandra Cassano20Giacomo Allegrini2111 Medical Oncology, ARCO Foundation, Cuneo, Italy2 Head and Neck Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy9 Candiolo Cancer Institute, Candiolo, Italy12 Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy14 Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy14 Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy10 Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy13 Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA1 Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy2 Head and Neck Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy1 Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy2 Head and Neck Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy1 Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy4 Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy5 Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Italy6 European Institute of Oncology, Milano, Italy7 University of Ljubljana, Ljubljana, Slovenia7 University of Ljubljana, Ljubljana, Slovenia3 Department of Oncology and Hemato-oncology, University of Milan, Milano, Italy15 Istituto Oncologico Veneto Istituto di Ricovero e Cura a Carattere Scientifico, Padova, Italy16 Policlinico Universitario Agostino Gemelli Dipartimento di scienze mediche e chirurgiche, Roma, Italy17 Azienda USL Toscana nord ovest Sede di Livorno, Pisa, ItalyBackground Immune checkpoint inhibitors have been approved and currently used in the clinical management of recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. The reported benefit in clinical trials is variable and heterogeneous. Our study aims at exploring and comparing the predictive role of gene-expression signatures with classical biomarkers for immunotherapy-treated R/M HNSCC patients in a multicentric phase IIIb trial.Methods Clinical data were prospectively collected in Nivactor tiral (single-arm, open-label, multicenter, phase IIIb clinical trial in platinum-refractory HNSCC treated with nivolumab). Findings were validated in an external independent cohort of immune-treated HNSCC patients, divided in long-term and short-term survivors (overall survival >18 and <6 months since the start of immunotherapy, respectively). Pretreatment tumor tissue specimen from immunotherapy-treated R/M HNSCC patients was used for PD-L1 (Tumor Proportion Score; Combined Positive Score (CPS)) and Tumor Mutational Burden (Oncopanel TSO500) evaluation and gene expression profiling; classical biomarkers and immune signatures (retrieved from literature) were challenged in the NIVACTOR dataset.Results Cluster-6 (Cl6) stratification of NIVACTOR cases in high score (n=16, 20%) and low score (n=64, 80%) demonstrated a statistically significant and clinically meaningful improvement in overall survival in the high-score cases (p=0.00028; HR=4.34, 95% CI 1.84 to 10.22) and discriminative ability reached area under the curve (AUC)=0.785 (95% CI 0.603 to 0.967). The association of high-score Cl6 with better outcome was also confirmed in: (1) NIVACTOR progression-free survival (p=4.93E-05; HR=3.71, 95% CI 1.92 to 7.18) and objective-response-rate (AUC=0.785; 95% CI 0.603 to 0.967); (2) long survivors versus short survivors (p=0.00544). In multivariate Cox regression analysis, Cl6 was independent from Eastern Cooperative Oncology Group performance status, PDL1-CPS, and primary tumor site.Conclusions These data highlight the presence of underlying biological differences able to predict survival and response following treatment with immunotherapy in platinum-refractory R/M HNSCC that could have translational implications improving treatment selection.Trial registration number EudraCT Number: 2017-000562-30.https://jitc.bmj.com/content/12/1/e007823.full |
| spellingShingle | Nerina Denaro Lisa Licitra Marco Merlano Francesco Perri Paolo Bossi Cristina Gurizzan Federica Perrone Athanassios Argiris Loris De Cecco Stefano Cavalieri Mara Serena Serafini Federico Pistore Deborah Lenoci Silvana Canevari Mario Airoldi Maria Cossu Rocca Primoz Strojan Cvetka Grasic Kuhar Andrea Vingiani Maria Grazia Ghi Alessandra Cassano Giacomo Allegrini Association of a gene-expression subtype to outcome and treatment response in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab Journal for ImmunoTherapy of Cancer |
| title | Association of a gene-expression subtype to outcome and treatment response in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab |
| title_full | Association of a gene-expression subtype to outcome and treatment response in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab |
| title_fullStr | Association of a gene-expression subtype to outcome and treatment response in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab |
| title_full_unstemmed | Association of a gene-expression subtype to outcome and treatment response in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab |
| title_short | Association of a gene-expression subtype to outcome and treatment response in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab |
| title_sort | association of a gene expression subtype to outcome and treatment response in patients with recurrent metastatic head and neck squamous cell carcinoma treated with nivolumab |
| url | https://jitc.bmj.com/content/12/1/e007823.full |
| work_keys_str_mv | AT nerinadenaro associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT lisalicitra associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT marcomerlano associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT francescoperri associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT paolobossi associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT cristinagurizzan associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT federicaperrone associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT athanassiosargiris associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT lorisdececco associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT stefanocavalieri associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT maraserenaserafini associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT federicopistore associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT deborahlenoci associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT silvanacanevari associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT marioairoldi associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT mariacossurocca associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT primozstrojan associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT cvetkagrasickuhar associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT andreavingiani associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT mariagraziaghi associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT alessandracassano associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab AT giacomoallegrini associationofageneexpressionsubtypetooutcomeandtreatmentresponseinpatientswithrecurrentmetastaticheadandnecksquamouscellcarcinomatreatedwithnivolumab |