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

被引：121

作者：

Verzoni, Elena ^{[1
]}

Carteni, Giacomo ^{[2
]}

Cortesi, Enrico ^{[3
]}

Giannarelli, Diana ^{[4
]}

De Giglio, Andrea ^{[5
]}

Sabbatini, Roberto ^{[6
]}

Buti, Sebastiano ^{[7
]}

Rossetti, Sabrina ^{[8
]}

Cognetti, Francesco ^{[9
]}

Rastelli, Francesca ^{[10
]}

Sobrero, Alberto ^{[11
]}

Turci, Daniele ^{[12
]}

Sternberg, Cora N. ^{[13
]}

Porta, Camillo ^{[14
,15
]}

Cappuzzo, Federico ^{[16
]}

Tortora, Giampaolo ^{[17
]}

Tassinari, Davide ^{[18
]}

Panni, Stefano ^{[19
]}

Pazzola, Antonio ^{[20
]}

Surico, Gianmarco ^{[21
]}

Raimondi, Alessandra ^{[1
]}

De Giorgi, Ugo ^{[22
]}

Procopio, Giuseppe ^{[1
]}

机构：

[1] Fdn IRCCS Ist Nazl Tumori Milano, Med Oncol Genitourinary Unit, Via Venezian 1, I-20133 Milan, Italy

[2] A Cardarelli Hosp, Oncol Unit, Naples, Italy

[3] Policlin Umberto 1, Radiol Oncol & Pathol, Rome, Italy

[4] IRCCS, Regina Elena Natl Canc Inst, Biostat Unit, Rome, Italy

[5] Azienda Osped Santa Maria, Med Oncol, Terni, Italy

[6] Azienda Osped Univ Policlin Modena, Oncol & Hematol Dept, Modena, Italy

[7] Azienda Osped Parma, Med Oncol, Parma, Italy

[8] Ist Nazl Tumori, Fdn Pascale, IRCCS, Urol & Gynecol, Naples, Italy

[9] Regina Elena Inst Canc Res, IRCCS, Med Oncol, Rome, Italy

[10] UOC Oncol, Med Oncol, Area Vasta 4, Fermo, Italy

[11] San Martino Hosp, Med Oncol, Genoa, Italy

[12] Osped Santa Maria Croci, Med Oncol, Ravenna, Italy

[13] Azienda Osped S Camillo Forlanini, Med Oncol, Rome, Italy

[14] Univ Pavia, Dept Internal Med, Pavia, Italy

[15] IRCCS Ist Clin Sci Maugeri, Div Translat Oncol, Pavia, Italy

[16] Osped Umberto AUSL Romagna, Med Oncol, Lugo, Italy

[17] AOU Integrata Verona Borgo Roma, Med Oncol, Verona, Italy

[18] Osped Infermi, Oncol, Rimini, Italy

[19] Ist Ospitalieri Cremona, Med Oncol, Cremona, Italy

[20] Osped Civile SS Annunziata, Med Oncol, Sassari, Italy

[21] Osped Vito Fazzi, Med Oncol, Lecce, Italy

[22] Ist Sci Romagnolo Studio & Cura Tumori IRST, Urol Gynecol Unit, Meldola, Italy

来源：

JOURNAL FOR IMMUNOTHERAPY OF CANCER | 2019年 / 7卷

关键词：

Immunotherapy; Adverse events; Renal cell carcinoma; Expanded access trials; IPILIMUMAB; EVEROLIMUS; REGRESSION; ANTIBODY;

D O I：

10.1186/s40425-019-0579-z

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 3mg/kg every 2weeks. 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 12months, the median progression-free survival was 4.5months (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 16.4months, p=0.01). Pts with irAEs versus without irAEs had a more significant survival benefit (median OS not reached versus 16.8months, p=0.002), confirmed at the landmark analysis at 6weeks. 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.ConclusionsThe appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab. Conclusions: The appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab.

引用

页数：9

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