Safety profile of nivolumab monotherapy

A pooled analysis of patients with advanced melanoma

Jeffrey S. Weber, F. Stephen Hodi, Jedd D. Wolchok, Suzanne Topalian, Dirk Schadendorf, James Larkin, Mario Sznol, Georgina V. Long, Hewei Li, Ian M. Waxman, Joel Jiang, Caroline Robert

Research output: Contribution to journalArticle

Abstract

Purpose: We conducted a retrospective analysis to assess the safety profile of nivolumab monotherapy in patients with advanced melanoma and describe the management of adverse events (AEs) using established safety guidelines. Patients and Methods: Safety data were pooled from four studies, including two phase III trials, with patients who received nivolumab 3 mg/kg once every 2 weeks. We evaluated rate of treatment-related AEs, time to onset and resolution of select AEs (those with potential immunologic etiology), and impact of select AEs and suppressive immune-modulating agents (IMs) on antitumor efficacy. Results: Among 576 patients, 71% (95% CI, 67% to 75%) experienced any-grade treatment-related AEs (most commonly fatigue [25%], pruritus [17%], diarrhea [13%], and rash [13%]), and 10% (95% CI, 8% to 13%) experienced grade 3 to 4 treatment-related AEs. No drug-related deaths were reported. Select AEs (occurring in 49% of patients) were most frequently skin related, GI, endocrine, and hepatic; grade 3 to 4 select AEs occurred in 4% of patients. Median time to onset of select AEs ranged from 5 weeks for skin to 15 weeks for renal AEs. Approximately 24% of patients received systemic IMs to manage select AEs, which in most cases resolved. Adjusting for number of doses, objective response rate (ORR) was significantly higher in patients who experienced treatment-related select AEs of any grade compared with those who did not. ORRs were similar in patients who did and patients who did not receive systemic IMs. Conclusion: Treatment-related AEs with nivolumab monotherapy were primarily low grade, and most resolved with established safety guidelines. Use of IMs did not affect ORR, although treatment-related select AEs of any grade were associated with higher ORR, but no progression-free survival benefit.

Original languageEnglish (US)
Pages (from-to)785-792
Number of pages8
JournalJournal of Clinical Oncology
Volume35
Issue number7
DOIs
StatePublished - Mar 1 2017

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Melanoma
Safety
Therapeutics
Guidelines
nivolumab
Skin
Pruritus
Patient Safety
Exanthema
Drug-Related Side Effects and Adverse Reactions
Disease-Free Survival
Fatigue
Diarrhea
Kidney
Liver

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Safety profile of nivolumab monotherapy : A pooled analysis of patients with advanced melanoma. / Weber, Jeffrey S.; Hodi, F. Stephen; Wolchok, Jedd D.; Topalian, Suzanne; Schadendorf, Dirk; Larkin, James; Sznol, Mario; Long, Georgina V.; Li, Hewei; Waxman, Ian M.; Jiang, Joel; Robert, Caroline.

In: Journal of Clinical Oncology, Vol. 35, No. 7, 01.03.2017, p. 785-792.

Research output: Contribution to journalArticle

Weber, JS, Hodi, FS, Wolchok, JD, Topalian, S, Schadendorf, D, Larkin, J, Sznol, M, Long, GV, Li, H, Waxman, IM, Jiang, J & Robert, C 2017, 'Safety profile of nivolumab monotherapy: A pooled analysis of patients with advanced melanoma', Journal of Clinical Oncology, vol. 35, no. 7, pp. 785-792. https://doi.org/10.1200/JCO.2015.66.1389
Weber, Jeffrey S. ; Hodi, F. Stephen ; Wolchok, Jedd D. ; Topalian, Suzanne ; Schadendorf, Dirk ; Larkin, James ; Sznol, Mario ; Long, Georgina V. ; Li, Hewei ; Waxman, Ian M. ; Jiang, Joel ; Robert, Caroline. / Safety profile of nivolumab monotherapy : A pooled analysis of patients with advanced melanoma. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 7. pp. 785-792.
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abstract = "Purpose: We conducted a retrospective analysis to assess the safety profile of nivolumab monotherapy in patients with advanced melanoma and describe the management of adverse events (AEs) using established safety guidelines. Patients and Methods: Safety data were pooled from four studies, including two phase III trials, with patients who received nivolumab 3 mg/kg once every 2 weeks. We evaluated rate of treatment-related AEs, time to onset and resolution of select AEs (those with potential immunologic etiology), and impact of select AEs and suppressive immune-modulating agents (IMs) on antitumor efficacy. Results: Among 576 patients, 71{\%} (95{\%} CI, 67{\%} to 75{\%}) experienced any-grade treatment-related AEs (most commonly fatigue [25{\%}], pruritus [17{\%}], diarrhea [13{\%}], and rash [13{\%}]), and 10{\%} (95{\%} CI, 8{\%} to 13{\%}) experienced grade 3 to 4 treatment-related AEs. No drug-related deaths were reported. Select AEs (occurring in 49{\%} of patients) were most frequently skin related, GI, endocrine, and hepatic; grade 3 to 4 select AEs occurred in 4{\%} of patients. Median time to onset of select AEs ranged from 5 weeks for skin to 15 weeks for renal AEs. Approximately 24{\%} of patients received systemic IMs to manage select AEs, which in most cases resolved. Adjusting for number of doses, objective response rate (ORR) was significantly higher in patients who experienced treatment-related select AEs of any grade compared with those who did not. ORRs were similar in patients who did and patients who did not receive systemic IMs. Conclusion: Treatment-related AEs with nivolumab monotherapy were primarily low grade, and most resolved with established safety guidelines. Use of IMs did not affect ORR, although treatment-related select AEs of any grade were associated with higher ORR, but no progression-free survival benefit.",
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