Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab

Suzanne Topalian, Mario Sznol, David F. McDermott, Harriet M. Kluger, Richard D. Carvajal, William Sharfman, Julie Brahmer, Donald P. Lawrence, Michael B. Atkins, John D. Powderly, Philip D. Leming, Evan Lipson, Igor Puzanov, David C. Smith, Janis M Taube, Jon M. Wigginton, Georgia D. Kollia, Ashok Gupta, Andrew Mark Pardoll, Jeffrey A. SosmanF. Stephen Hodi

Research output: Contribution to journalArticle

Abstract

Purpose: Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued. Patients and Methods: Patients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation. Results: Median overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative. Conclusion: Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.

Original languageEnglish (US)
Pages (from-to)1020-1030
Number of pages11
JournalJournal of Clinical Oncology
Volume32
Issue number10
DOIs
StatePublished - Apr 1 2014

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Patient Safety
Melanoma
Survival
Neoplasms
Therapeutics
Cell Death
nivolumab
Safety
Disease Progression
Outpatients
Survival Rate
Randomized Controlled Trials
Maintenance
T-Lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. / Topalian, Suzanne; Sznol, Mario; McDermott, David F.; Kluger, Harriet M.; Carvajal, Richard D.; Sharfman, William; Brahmer, Julie; Lawrence, Donald P.; Atkins, Michael B.; Powderly, John D.; Leming, Philip D.; Lipson, Evan; Puzanov, Igor; Smith, David C.; Taube, Janis M; Wigginton, Jon M.; Kollia, Georgia D.; Gupta, Ashok; Pardoll, Andrew Mark; Sosman, Jeffrey A.; Hodi, F. Stephen.

In: Journal of Clinical Oncology, Vol. 32, No. 10, 01.04.2014, p. 1020-1030.

Research output: Contribution to journalArticle

Topalian, S, Sznol, M, McDermott, DF, Kluger, HM, Carvajal, RD, Sharfman, W, Brahmer, J, Lawrence, DP, Atkins, MB, Powderly, JD, Leming, PD, Lipson, E, Puzanov, I, Smith, DC, Taube, JM, Wigginton, JM, Kollia, GD, Gupta, A, Pardoll, AM, Sosman, JA & Hodi, FS 2014, 'Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab', Journal of Clinical Oncology, vol. 32, no. 10, pp. 1020-1030. https://doi.org/10.1200/JCO.2013.53.0105
Topalian, Suzanne ; Sznol, Mario ; McDermott, David F. ; Kluger, Harriet M. ; Carvajal, Richard D. ; Sharfman, William ; Brahmer, Julie ; Lawrence, Donald P. ; Atkins, Michael B. ; Powderly, John D. ; Leming, Philip D. ; Lipson, Evan ; Puzanov, Igor ; Smith, David C. ; Taube, Janis M ; Wigginton, Jon M. ; Kollia, Georgia D. ; Gupta, Ashok ; Pardoll, Andrew Mark ; Sosman, Jeffrey A. ; Hodi, F. Stephen. / Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 10. pp. 1020-1030.
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abstract = "Purpose: Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued. Patients and Methods: Patients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation. Results: Median overall survival in nivolumab-treated patients (62{\%} with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62{\%} and 43{\%}, respectively. Among 33 patients with objective tumor regressions (31{\%}), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71{\%}) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative. Conclusion: Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.",
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AU - Topalian, Suzanne

AU - Sznol, Mario

AU - McDermott, David F.

AU - Kluger, Harriet M.

AU - Carvajal, Richard D.

AU - Sharfman, William

AU - Brahmer, Julie

AU - Lawrence, Donald P.

AU - Atkins, Michael B.

AU - Powderly, John D.

AU - Leming, Philip D.

AU - Lipson, Evan

AU - Puzanov, Igor

AU - Smith, David C.

AU - Taube, Janis M

AU - Wigginton, Jon M.

AU - Kollia, Georgia D.

AU - Gupta, Ashok

AU - Pardoll, Andrew Mark

AU - Sosman, Jeffrey A.

AU - Hodi, F. Stephen

PY - 2014/4/1

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N2 - Purpose: Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued. Patients and Methods: Patients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation. Results: Median overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative. Conclusion: Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.

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