PMID- 28068177
OWN - NLM
STAT- MEDLINE
DCOM- 20170802
LR  - 20220409
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 35
IP  - 7
DP  - 2017 Mar
TI  - Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With 
      Advanced Melanoma.
PG  - 785-792
LID - 10.1200/JCO.2015.66.1389 [doi]
AB  - 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.
FAU - Weber, Jeffrey S
AU  - Weber JS
AD  - Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, 
      Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel 
      Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale 
      University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, 
      New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, 
      Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James 
      Larkin, Royal Marsden National Health Service Foundation Trust, London, United 
      Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, 
      Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and 
      Paris-Sud University, Villejuif-Paris Sud, France.
FAU - Hodi, F Stephen
AU  - Hodi FS
AD  - Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, 
      Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel 
      Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale 
      University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, 
      New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, 
      Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James 
      Larkin, Royal Marsden National Health Service Foundation Trust, London, United 
      Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, 
      Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and 
      Paris-Sud University, Villejuif-Paris Sud, France.
FAU - Wolchok, Jedd D
AU  - Wolchok JD
AD  - Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, 
      Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel 
      Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale 
      University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, 
      New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, 
      Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James 
      Larkin, Royal Marsden National Health Service Foundation Trust, London, United 
      Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, 
      Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and 
      Paris-Sud University, Villejuif-Paris Sud, France.
FAU - Topalian, Suzanne L
AU  - Topalian SL
AD  - Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, 
      Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel 
      Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale 
      University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, 
      New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, 
      Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James 
      Larkin, Royal Marsden National Health Service Foundation Trust, London, United 
      Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, 
      Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and 
      Paris-Sud University, Villejuif-Paris Sud, France.
FAU - Schadendorf, Dirk
AU  - Schadendorf D
AD  - Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, 
      Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel 
      Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale 
      University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, 
      New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, 
      Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James 
      Larkin, Royal Marsden National Health Service Foundation Trust, London, United 
      Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, 
      Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and 
      Paris-Sud University, Villejuif-Paris Sud, France.
FAU - Larkin, James
AU  - Larkin J
AD  - Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, 
      Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel 
      Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale 
      University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, 
      New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, 
      Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James 
      Larkin, Royal Marsden National Health Service Foundation Trust, London, United 
      Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, 
      Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and 
      Paris-Sud University, Villejuif-Paris Sud, France.
FAU - Sznol, Mario
AU  - Sznol M
AD  - Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, 
      Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel 
      Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale 
      University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, 
      New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, 
      Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James 
      Larkin, Royal Marsden National Health Service Foundation Trust, London, United 
      Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, 
      Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and 
      Paris-Sud University, Villejuif-Paris Sud, France.
FAU - Long, Georgina V
AU  - Long GV
AD  - Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, 
      Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel 
      Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale 
      University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, 
      New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, 
      Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James 
      Larkin, Royal Marsden National Health Service Foundation Trust, London, United 
      Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, 
      Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and 
      Paris-Sud University, Villejuif-Paris Sud, France.
FAU - Li, Hewei
AU  - Li H
AD  - Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, 
      Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel 
      Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale 
      University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, 
      New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, 
      Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James 
      Larkin, Royal Marsden National Health Service Foundation Trust, London, United 
      Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, 
      Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and 
      Paris-Sud University, Villejuif-Paris Sud, France.
FAU - Waxman, Ian M
AU  - Waxman IM
AD  - Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, 
      Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel 
      Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale 
      University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, 
      New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, 
      Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James 
      Larkin, Royal Marsden National Health Service Foundation Trust, London, United 
      Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, 
      Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and 
      Paris-Sud University, Villejuif-Paris Sud, France.
FAU - Jiang, Joel
AU  - Jiang J
AD  - Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, 
      Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel 
      Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale 
      University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, 
      New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, 
      Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James 
      Larkin, Royal Marsden National Health Service Foundation Trust, London, United 
      Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, 
      Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and 
      Paris-Sud University, Villejuif-Paris Sud, France.
FAU - Robert, Caroline
AU  - Robert C
AD  - Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, 
      Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel 
      Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale 
      University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, 
      New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, 
      Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James 
      Larkin, Royal Marsden National Health Service Foundation Trust, London, United 
      Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, 
      Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and 
      Paris-Sud University, Villejuif-Paris Sud, France.
LA  - eng
PT  - Journal Article
DEP - 20161114
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antineoplastic Agents)
RN  - 31YO63LBSN (Nivolumab)
SB  - IM
CIN - J Clin Oncol. 2017 Jun 10;35(17):1968. PMID: 28591545
CIN - J Clin Oncol. 2017 Jun 10;35(17):1967-1968. PMID: 28591546
MH  - Antibodies, Monoclonal/*administration & dosage/*adverse effects
MH  - Antineoplastic Agents/administration & dosage/adverse effects
MH  - Clinical Trials, Phase I as Topic
MH  - Clinical Trials, Phase III as Topic
MH  - Humans
MH  - Melanoma/*drug therapy
MH  - Nivolumab
MH  - Retrospective Studies
MH  - Skin Neoplasms/drug therapy
EDAT- 2017/01/10 06:00
MHDA- 2017/08/03 06:00
CRDT- 2017/01/10 06:00
PHST- 2017/01/10 06:00 [pubmed]
PHST- 2017/08/03 06:00 [medline]
PHST- 2017/01/10 06:00 [entrez]
AID - 10.1200/JCO.2015.66.1389 [pii]
AID - 10.1200/JCO.2015.66.1389 [doi]
PST - ppublish
SO  - J Clin Oncol. 2017 Mar;35(7):785-792. doi: 10.1200/JCO.2015.66.1389. Epub 2016 
      Nov 14.