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 language | English |
|---|---|
| Article number | 99 |
| Journal | Journal for ImmunoTherapy of Cancer |
| Volume | 7 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Apr 3 2019 |
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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 journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=85063937275&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063937275&partnerID=8YFLogxK
U2 - 10.1186/s40425-019-0579-z
DO - 10.1186/s40425-019-0579-z
M3 - Article
C2 - 30944023
AN - SCOPUS:85063937275
VL - 7
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
SN - 2051-1426
IS - 1
M1 - 99
ER -