Survival, durable response, and long-term safety in patients with previously treated advanced renal cell carcinoma receiving nivolumab

David F. McDermott, Toni K. Choueiri, Igor Puzanov, Stephen Hodi, Charles G. Drake, Julie R. Brahmer, Hans J. Hammers, Suzanne L. Topalian, Drew M. Pardoll, Mario Sznol, John D. Powderly, David C. Smith, Richard D. Carvajal, Jon M. Wigginton, Georgia D. Kollia, Ashok Gupta, Dan McDonald, Vindira Sankar, Jeffrey A. Sosman, Michael B. Atkins

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Abstract

Purpose: Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts. Patients and Methods: A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation. Results: Ten patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible. Conclusion: Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC.

Original languageEnglish (US)
Pages (from-to)2013-2020
Number of pages8
JournalJournal of Clinical Oncology
Volume33
Issue number18
DOIs
StatePublished - Jun 20 2015

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Patient Safety
Renal Cell Carcinoma
Survival
Therapeutics
nivolumab
Immunoglobulins
Neoplasms
Outpatients
Survival Rate
Randomized Controlled Trials
Antibodies

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

McDermott, D. F., Choueiri, T. K., Puzanov, I., Hodi, S., Drake, C. G., Brahmer, J. R., ... Atkins, M. B. (2015). Survival, durable response, and long-term safety in patients with previously treated advanced renal cell carcinoma receiving nivolumab. Journal of Clinical Oncology, 33(18), 2013-2020. https://doi.org/10.1200/JCO.2014.58.1041

Survival, durable response, and long-term safety in patients with previously treated advanced renal cell carcinoma receiving nivolumab. / McDermott, David F.; Choueiri, Toni K.; Puzanov, Igor; Hodi, Stephen; Drake, Charles G.; Brahmer, Julie R.; Hammers, Hans J.; Topalian, Suzanne L.; Pardoll, Drew M.; Sznol, Mario; Powderly, John D.; Smith, David C.; Carvajal, Richard D.; Wigginton, Jon M.; Kollia, Georgia D.; Gupta, Ashok; McDonald, Dan; Sankar, Vindira; Sosman, Jeffrey A.; Atkins, Michael B.

In: Journal of Clinical Oncology, Vol. 33, No. 18, 20.06.2015, p. 2013-2020.

Research output: Contribution to journalArticle

McDermott, DF, Choueiri, TK, Puzanov, I, Hodi, S, Drake, CG, Brahmer, JR, Hammers, HJ, Topalian, SL, Pardoll, DM, Sznol, M, Powderly, JD, Smith, DC, Carvajal, RD, Wigginton, JM, Kollia, GD, Gupta, A, McDonald, D, Sankar, V, Sosman, JA & Atkins, MB 2015, 'Survival, durable response, and long-term safety in patients with previously treated advanced renal cell carcinoma receiving nivolumab', Journal of Clinical Oncology, vol. 33, no. 18, pp. 2013-2020. https://doi.org/10.1200/JCO.2014.58.1041
McDermott, David F. ; Choueiri, Toni K. ; Puzanov, Igor ; Hodi, Stephen ; Drake, Charles G. ; Brahmer, Julie R. ; Hammers, Hans J. ; Topalian, Suzanne L. ; Pardoll, Drew M. ; Sznol, Mario ; Powderly, John D. ; Smith, David C. ; Carvajal, Richard D. ; Wigginton, Jon M. ; Kollia, Georgia D. ; Gupta, Ashok ; McDonald, Dan ; Sankar, Vindira ; Sosman, Jeffrey A. ; Atkins, Michael B. / Survival, durable response, and long-term safety in patients with previously treated advanced renal cell carcinoma receiving nivolumab. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 18. pp. 2013-2020.
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abstract = "Purpose: Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts. Patients and Methods: A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation. Results: Ten patients (29{\%}) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27{\%}) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks. Median overall survival in all patients (71{\%} with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71{\%}, 48{\%}, and 44{\%}, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18{\%} of patients; all were reversible. Conclusion: Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC.",
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AU - McDermott, David F.

AU - Choueiri, Toni K.

AU - Puzanov, Igor

AU - Hodi, Stephen

AU - Drake, Charles G.

AU - Brahmer, Julie R.

AU - Hammers, Hans J.

AU - Topalian, Suzanne L.

AU - Pardoll, Drew M.

AU - Sznol, Mario

AU - Powderly, John D.

AU - Smith, David C.

AU - Carvajal, Richard D.

AU - Wigginton, Jon M.

AU - Kollia, Georgia D.

AU - Gupta, Ashok

AU - McDonald, Dan

AU - Sankar, Vindira

AU - Sosman, Jeffrey A.

AU - Atkins, Michael B.

PY - 2015/6/20

Y1 - 2015/6/20

N2 - Purpose: Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts. Patients and Methods: A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation. Results: Ten patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible. Conclusion: Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC.

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