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

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 SuricoAlessandra Raimondi, Ugo De Giorgi, Giuseppe Procopio

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number99
JournalJournal for ImmunoTherapy of Cancer
Volume7
Issue number1
DOIs
Publication statusPublished - Apr 3 2019

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Renal Cell Carcinoma
Drug-Related Side Effects and Adverse Reactions
Safety
Survival
Logistic Models
Lung
Skin
Liver
nivolumab
Immunotherapy
Disease-Free Survival
Survival Rate
Therapeutics
Population

Keywords

  • Adverse events
  • Expanded access trials
  • Immunotherapy
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

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. / Verzoni, Elena; Cartenì, Giacomo; Cortesi, Enrico; Giannarelli, Diana; De Giglio, Andrea; Sabbatini, Roberto; Buti, Sebastiano; Rossetti, Sabrina; Cognetti, Francesco; Rastelli, Francesca; Sobrero, Alberto; Turci, Daniele; Sternberg, Cora N.; Porta, Camillo; Cappuzzo, Federico; Tortora, Giampaolo; Tassinari, Davide; Panni, Stefano; Pazzola, Antonio; Surico, Gianmarco; Raimondi, Alessandra; De Giorgi, Ugo; Procopio, Giuseppe.

In: Journal for ImmunoTherapy of Cancer, Vol. 7, No. 1, 99, 03.04.2019.

Research output: Contribution to journalArticle

Verzoni, Elena ; Cartenì, Giacomo ; Cortesi, Enrico ; Giannarelli, Diana ; De Giglio, Andrea ; Sabbatini, Roberto ; Buti, Sebastiano ; Rossetti, Sabrina ; Cognetti, Francesco ; Rastelli, Francesca ; Sobrero, Alberto ; Turci, Daniele ; Sternberg, Cora N. ; Porta, Camillo ; Cappuzzo, Federico ; Tortora, Giampaolo ; Tassinari, Davide ; Panni, Stefano ; Pazzola, Antonio ; Surico, Gianmarco ; Raimondi, Alessandra ; De Giorgi, Ugo ; Procopio, Giuseppe. / 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. In: Journal for ImmunoTherapy of Cancer. 2019 ; Vol. 7, No. 1.
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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.",
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author = "Elena Verzoni and Giacomo Carten{\`i} and Enrico Cortesi and Diana Giannarelli and {De Giglio}, Andrea and Roberto Sabbatini and Sebastiano Buti and Sabrina Rossetti and Francesco Cognetti and Francesca Rastelli and Alberto Sobrero and Daniele Turci and Sternberg, {Cora N.} and Camillo Porta and Federico Cappuzzo and Giampaolo Tortora and Davide Tassinari and Stefano Panni and Antonio Pazzola and Gianmarco Surico and Alessandra Raimondi and {De Giorgi}, Ugo and Giuseppe Procopio",
year = "2019",
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journal = "Journal for ImmunoTherapy of Cancer",
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TY - JOUR

T1 - Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival

T2 - The Italian expanded access program

AU - Verzoni, Elena

AU - Cartenì, Giacomo

AU - Cortesi, Enrico

AU - Giannarelli, Diana

AU - De Giglio, Andrea

AU - Sabbatini, Roberto

AU - Buti, Sebastiano

AU - Rossetti, Sabrina

AU - Cognetti, Francesco

AU - Rastelli, Francesca

AU - Sobrero, Alberto

AU - Turci, Daniele

AU - Sternberg, Cora N.

AU - Porta, Camillo

AU - Cappuzzo, Federico

AU - Tortora, Giampaolo

AU - Tassinari, Davide

AU - Panni, Stefano

AU - Pazzola, Antonio

AU - Surico, Gianmarco

AU - Raimondi, Alessandra

AU - De Giorgi, Ugo

AU - Procopio, Giuseppe

PY - 2019/4/3

Y1 - 2019/4/3

N2 - 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.

AB - 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.

KW - Adverse events

KW - Expanded access trials

KW - Immunotherapy

KW - Renal cell carcinoma

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U2 - 10.1186/s40425-019-0579-z

DO - 10.1186/s40425-019-0579-z

M3 - Article

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JO - Journal for ImmunoTherapy of Cancer

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