Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program
Abstract Background The Italian Renal Cell Cancer Early Access Program was an expanded access program that allowed access to nivolumab, for patients (pts) with metastatic renal cell carcinoma (mRCC) prior to regulatory approval. Methods Pts with previously treated advanced or mRCC were eligible to r...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2019-04-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40425-019-0579-z |
| _version_ | 1818324529066278912 |
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| author | Elena Verzoni Giacomo Cartenì Enrico Cortesi Diana Giannarelli Andrea De Giglio Roberto Sabbatini Sebastiano Buti Sabrina Rossetti Francesco Cognetti Francesca Rastelli Alberto Sobrero Daniele Turci Cora N. Sternberg Camillo Porta Federico Cappuzzo Giampaolo Tortora Davide Tassinari Stefano Panni Antonio Pazzola Gianmarco Surico Alessandra Raimondi Ugo De Giorgi Giuseppe Procopio on behalf of the Italian Nivolumab Renal Cell Cancer Early Access Program group |
| author_facet | Elena Verzoni Giacomo Cartenì Enrico Cortesi Diana Giannarelli Andrea De Giglio Roberto Sabbatini Sebastiano Buti Sabrina Rossetti Francesco Cognetti Francesca Rastelli Alberto Sobrero Daniele Turci Cora N. Sternberg Camillo Porta Federico Cappuzzo Giampaolo Tortora Davide Tassinari Stefano Panni Antonio Pazzola Gianmarco Surico Alessandra Raimondi Ugo De Giorgi Giuseppe Procopio on behalf of the Italian Nivolumab Renal Cell Cancer Early Access Program group |
| author_sort | Elena Verzoni |
| collection | DOAJ |
| description | Abstract Background The Italian Renal Cell Cancer Early Access Program was an expanded access program that allowed access to nivolumab, for patients (pts) with metastatic renal cell carcinoma (mRCC) prior to regulatory approval. Methods Pts with previously treated advanced or mRCC were eligible to receive nivolumab 3 mg/kg every 2 weeks. Pts included in the analysis had received ≥1 dose of nivolumab and were monitored for drug-related adverse events (drAEs) using CTCAE v.4.0. Immune-related (ir) AEs were defined as AEs displaying a certain, likely or possible correlation with immunotherapy (cutaneous, endocrine, hepatic, gastro-intestinal and pulmonary). The association between overall survival (OS) and irAEs was assessed, and associations between variables were evaluated with a logistic regression model. Results A total of 389 pts were enrolled between July 2015 and April 2016. Overall, the objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% CI 3.7–6.2) and the 12-month overall survival rate was 63%. Any grade and grade 3–4 drAEs were reported in 124 (32%) and 27 (7%) of pts, respectively, and there were no treatment-related deaths. Any grade irAEs occurred in 76 (20%) of patients, 8% cutaneous, 4% endocrine, 2% hepatic, 5% gastro-intestinal and 1% pulmonary. Of the 22 drAEs inducing treatment discontinuation, 10 (45%) were irAEs. Pts with drAEs had a significantly longer survival than those without drAEs (median OS 22.5 versus 16.4 months, p = 0.01). Pts with irAEs versus without irAEs had a more significant survival benefit (median OS not reached versus 16.8 months, p = 0.002), confirmed at the landmark analysis at 6 weeks. The occurrence of irAEs displayed a strong association with OS in univariable (HR 0.48, p = 0.003) and multivariable (HR 0.57, p = 0.02) analysis. Conclusions The appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab. |
| first_indexed | 2024-12-13T11:30:02Z |
| format | Article |
| id | doaj.art-8dc2e19ba5544857a0d837544b55b59a |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-12-13T11:30:02Z |
| publishDate | 2019-04-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-8dc2e19ba5544857a0d837544b55b59a2022-12-21T23:47:58ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262019-04-01711910.1186/s40425-019-0579-zReal-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access programElena Verzoni0Giacomo Cartenì1Enrico Cortesi2Diana Giannarelli3Andrea De Giglio4Roberto Sabbatini5Sebastiano Buti6Sabrina Rossetti7Francesco Cognetti8Francesca Rastelli9Alberto Sobrero10Daniele Turci11Cora N. Sternberg12Camillo Porta13Federico Cappuzzo14Giampaolo Tortora15Davide Tassinari16Stefano Panni17Antonio Pazzola18Gianmarco Surico19Alessandra Raimondi20Ugo De Giorgi21Giuseppe Procopio22on behalf of the Italian Nivolumab Renal Cell Cancer Early Access Program groupMedical Oncology-Genitourinary Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di MilanoOncology Unit, A. Cardarelli HospitalRadiology, Oncology and Pathology, Policlinico Umberto IBiostatistical Unit, Regina Elena National Cancer Institute – IRCCSMedical Oncology, Azienda Ospedaliera Santa MariaOncology and Hematology Department, Azienda Ospedaliero-Universitaria Policlinico di ModenaMedical Oncology, Azienda Ospedaliera di ParmaUrology and Gynecology, Istituto Nazionale Tumori – IRCCS – Fondazione PascaleMedical Oncology, Regina Elena National Cancer Institute – IRCCSMedical OncologyMedical Oncology, San Martino HospitalMedical Oncology, Ospedale Santa Maria delle CrociMedical Oncology, Azienda Ospedaliera S. Camillo ForlaniniDepartment of Internal Medicine, University of Pavia and Division of Translational Oncology, IRCCS Istituti Clinici Scientifici MaugeriMedical Oncology, Ospedale Umberto I (AUSL Romagna)Medical Oncology, AOU Integrata Verona “Borgo Roma”Oncology, Ospedale InfermiMedical Oncology, Istituti Ospitalieri di CremonaMedical Oncology, Ospedale Civile SS AnnunziataMedical Oncology, Ospedale Vito FazziMedical Oncology-Genitourinary Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di MilanoUrologic-Gynecologic Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)Medical Oncology-Genitourinary Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di MilanoAbstract Background The Italian Renal Cell Cancer Early Access Program was an expanded access program that allowed access to nivolumab, for patients (pts) with metastatic renal cell carcinoma (mRCC) prior to regulatory approval. Methods Pts with previously treated advanced or mRCC were eligible to receive nivolumab 3 mg/kg every 2 weeks. Pts included in the analysis had received ≥1 dose of nivolumab and were monitored for drug-related adverse events (drAEs) using CTCAE v.4.0. Immune-related (ir) AEs were defined as AEs displaying a certain, likely or possible correlation with immunotherapy (cutaneous, endocrine, hepatic, gastro-intestinal and pulmonary). The association between overall survival (OS) and irAEs was assessed, and associations between variables were evaluated with a logistic regression model. Results A total of 389 pts were enrolled between July 2015 and April 2016. Overall, the objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% CI 3.7–6.2) and the 12-month overall survival rate was 63%. Any grade and grade 3–4 drAEs were reported in 124 (32%) and 27 (7%) of pts, respectively, and there were no treatment-related deaths. Any grade irAEs occurred in 76 (20%) of patients, 8% cutaneous, 4% endocrine, 2% hepatic, 5% gastro-intestinal and 1% pulmonary. Of the 22 drAEs inducing treatment discontinuation, 10 (45%) were irAEs. Pts with drAEs had a significantly longer survival than those without drAEs (median OS 22.5 versus 16.4 months, p = 0.01). Pts with irAEs versus without irAEs had a more significant survival benefit (median OS not reached versus 16.8 months, p = 0.002), confirmed at the landmark analysis at 6 weeks. The occurrence of irAEs displayed a strong association with OS in univariable (HR 0.48, p = 0.003) and multivariable (HR 0.57, p = 0.02) analysis. Conclusions The appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab.http://link.springer.com/article/10.1186/s40425-019-0579-zImmunotherapyAdverse eventsRenal cell carcinomaExpanded access trials |
| spellingShingle | Elena Verzoni Giacomo Cartenì Enrico Cortesi Diana Giannarelli Andrea De Giglio Roberto Sabbatini Sebastiano Buti Sabrina Rossetti Francesco Cognetti Francesca Rastelli Alberto Sobrero Daniele Turci Cora N. Sternberg Camillo Porta Federico Cappuzzo Giampaolo Tortora Davide Tassinari Stefano Panni Antonio Pazzola Gianmarco Surico Alessandra Raimondi Ugo De Giorgi Giuseppe Procopio on behalf of the Italian Nivolumab Renal Cell Cancer Early Access Program group Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program Journal for ImmunoTherapy of Cancer Immunotherapy Adverse events Renal cell carcinoma Expanded access trials |
| title | Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program |
| title_full | Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program |
| title_fullStr | Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program |
| title_full_unstemmed | Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program |
| title_short | Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program |
| title_sort | real world efficacy and safety of nivolumab in previously treated metastatic renal cell carcinoma and association between immune related adverse events and survival the italian expanded access program |
| topic | Immunotherapy Adverse events Renal cell carcinoma Expanded access trials |
| url | http://link.springer.com/article/10.1186/s40425-019-0579-z |
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