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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
Open accessAbstract
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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“Patients who experienced IRAEs had prolonged OS compared to those who did not experience them (NR vs 16.8 months, p = .002).”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [40]
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“In the included patients, 20% experienced any IRAEs with the most common sites being dermatologic (8%), gastrointestinal (5%) and endocrine (4%).”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [40]
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“In terms of 1-year OS, 1-year OS was 75.4 and 59.8% in patients who did and did not experience IRAEs, respectively.”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [40]
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Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma
Motzer, R. J., Escudier, B., McDermott, D. F., George, S., Hammers, H. J., Srinivas, S., Tykodi, S. S., Sosman, J. A., Procopio, G., Plimack, E. R., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1510665 · Cited by 5,807
Self-citationBrahmer, J. R., Lacchetti, C., Schneider, B. J., Atkins, M. B., Brassil, K. J., Caterino, J. M., Chau, I., Ernstoff, M. S., Gardner, J. M., Ginex, P., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.77.6385 · Cited by 3,713
Immune-related adverse events with immune checkpoint blockade: a comprehensive review
Michot, J. M., Bigenwald, C., Champiat, S., Collins, M., Carbonnel, F., Postel-Vinay, S., Berdelou, A., Varga, A., Bahleda, R., Hollebecque, A., et al. (2016) · European Journal of Cancer · doi:10.1016/j.ejca.2015.11.016 · Cited by 2,127
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Horvat, T. Z., Adel, N. G., Dang, T.-O., Momtaz, P., Postow, M. A., Callahan, M. K., Carvajal, R. D., Dickson, M. A., D'Angelo, S. P., Woo, K. M., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.60.8448 · Cited by 1,064
Attia, P., Phan, G. Q., Maker, A. V., Robinson, M. R., Quezado, M. M., Yang, J. C., Sherry, R. M., Topalian, S. L., Kammula, U. S., Royal, R. E., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.06.205 · Cited by 1,012
Freeman-Keller, M., Kim, Y., Cronin, H., Richards, A., Gibney, G., & Weber, J. S. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1136 · Cited by 863
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Lefort, F., Dalban, C., Gross‐Goupil, M., Laguerre, B., Chabaud, S., Escudier, B. J., & Albiges, L. K. (2023) · JAMA Oncology · doi:10.1001/jamaoncol.2023.2296 · Cited by 5
Jiao, R., Wang, C.-Y., Ying, H., Nie, M., Leng, J., Liu, Y., Zhang, Z., Zhou, N., & Bai, C. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1679328 · Cited by 4
Polcaro, G., Liguori, L., Manzo, V., Bellis, E. D., Stefanelli, B., Pagliara, V., Langella, M., Caputo, A., Ottaiano, A., Martinelli, R., et al. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2025-012207 · Cited by 3
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Rodler, S., Tamalunas, A. J., Schulz, G. B., Apfelbeck, M., Götz, M., Berg, E. K., Stief, C. G., & Casuscelli, J. (2022) · Uro-News · doi:10.1007/s00092-022-5501-1
Tansir, G., Baskarane, H., & Batra, A. (2025) · Cancer Research Statistics and Treatment · doi:10.4103/crst.crst_259_24
Chalif, J., Morton, M. A., McLaughlin, E. M., Gonzalez, A., Fulton, J., Sciuva, J., Marcu, I., Bixel, K. L., Cohn, D. E., Cosgrove, C. M., et al. (2025) · Gynecologic Oncology Reports · doi:10.1016/j.gore.2025.101782
Zhao, C., Liu, H., Wang, A., Zhai, B., Jiang, B., Hu, L., Yu, H., Bai, C., & Chen, K. (2025) · Medicine · doi:10.1097/md.0000000000043153
Sakurai, K., Imaue, S., Ikeda, A., Sakurai, A., Tachinami, H., Takatsuka, D., Fujiki, M., & Yamada, S. (2025) · Journal of Oral and Maxillofacial Surgery Medicine and Pathology · doi:10.1016/j.ajoms.2025.09.015
Волкова, М. И., Nersesova, T. A., Lyadova, M. A., Kuzmina, E., Antonova, T. G., Царева, Е. В., Стативко, О. А., Черняев, В. А., & Покатаев, И. А. (2025) · Malignant tumours · doi:10.18027/2224-5057-2025-050
Carter, E. R., & Lee, J. M. (2021) · Archive of International Journal of Cancer and Allied Science · doi:10.51847/ayetm32nyo
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Metadata
- Authors
- on behalf of the Italian Nivolumab Renal Cell Cancer Early Access Program group, Verzoni, E., Cartenì, G., Cortesi, E., Giannarelli, D., De Giglio, A., Sabbatini, R., Buti, S., Rossetti, S., Cognetti, F., Rastelli, F., Sobrero, A., Turci, D., Sternberg, C. N., Porta, C., Cappuzzo, F., Tortora, G., Tassinari, D., Panni, S., Pazzola, A., Surico, G., Raimondi, A., De Giorgi, U., & Procopio, G.
- Affiliations
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Ospedale Antonio Cardarelli (IT)
- Policlinico Umberto I (IT)
- Azienda Ospedaliera S.Maria (IT)
- Azienda Ospedaliero-Universitaria di Modena (IT)
- Ospedale di Parma (IT)
- Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Ospedale Policlinico San Martino (IT)
- Ospedale "Santa Maria delle Croci" di Ravenna (IT)
- University of Pavia (IT)
- Azienda Ospedaliera Universitaria Integrata Verona (IT)
- Ospedale Infermi di Rimini (IT)
- Istituti Ospitalieri di Cremona (IT)
- Ospedale Vito Fazzi (IT)
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT)
- Corresponding author
- on behalf of the Italian Nivolumab Renal Cell Cancer Early Access Program group
- ORCID
- Venue
- Journal for ImmunoTherapy of Cancer
- Publisher
- BMJ
- Published
- 2019-04-03
- Volume
- 7
- Issue
- 1
- Pages
- 99-99
- ISSN
- 2051-1426 (ISSN-L)
- PMC
- PMC6448290
- OpenAlex
- W2942674623
- Cited by
- 140
- References
- 30
- Citations by year
- 2026: 2 · 2025: 14 · 2024: 12 · 2023: 14 · 2022: 29 · 2021: 38 · 2020: 23 · 2019: 8
- FWCI
- 10.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal for ImmunoTherapy of Cancer (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, other-oa)
- Funders
- Bristol-Myers Squibb (not applicable)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Keywords
- nivolumab, metastatic renal cell carcinoma, immune-related adverse events, expanded access program, overall survival, drug-related adverse events, immune checkpoint inhibitors, treatment discontinuation, progression-free survival, objective response rate, cutaneous adverse events, endocrine adverse events, hepatic adverse events, pulmonary adverse events, previously treated patients, real-world efficacy and safety
- MeSH terms
- Antineoplastic Agents, Immunological, Nivolumab, Progression-Free Survival, Adult, Aged, Aged, 80 and over, Carcinoma, Renal Cell, Female, Follow-Up Studies, Humans, Italy, Kidney Neoplasms, Male, Middle Aged, Neoplasm Recurrence, Local, Severity of Illness Index, Survival Rate, Drug-Related Side Effects and Adverse Reactions
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