PMID- 29106665
OWN - NLM
STAT- MEDLINE
DCOM- 20190116
LR  - 20240314
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 20
IP  - 5
DP  - 2018 Apr 9
TI  - Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: 
      results from exploratory phase I cohorts of CheckMate 143.
PG  - 674-686
LID - 10.1093/neuonc/nox208 [doi]
AB  - BACKGROUND: Immunotherapies have demonstrated efficacy across a diverse set of 
      tumors supporting further evaluation in glioblastoma. The objective of this study 
      was to evaluate the safety/tolerability and describe immune-mediated effects of 
      nivolumab +/- ipilimumab in patients with recurrent glioblastoma. Exploratory 
      efficacy outcomes are also reported. METHODS: Patients were randomized to receive 
      nivolumab 3 mg/kg every 2 weeks (Q2W; NIVO3) or nivolumab 1 mg/kg + ipilimumab 3 
      mg/kg every 3 weeks (Q3W) for 4 doses, then nivolumab 3 mg/kg Q2W (NIVO1+IPI3). 
      An alternative regimen of nivolumab 3 mg/kg + ipilimumab 1 mg/kg Q3W for 4 doses, 
      then nivolumab 3 mg/kg Q2W (NIVO3+IPI1) was investigated in a nonrandomized arm. 
      RESULTS: Forty patients were enrolled (NIVO3, n = 10; NIVO1+IPI3, n = 10; 
      NIVO3+IPI1, n = 20). The most common treatment-related adverse events (AEs) were 
      fatigue (NIVO3, 30%; NIVO1+IPI3, 80%; NIVO3+IPI1, 55%) and diarrhea (10%, 70%, 
      30%, respectively). AEs leading to discontinuation occurred in 10% (NIVO3), 30% 
      (NIVO1+IPI3), and 20% (NIVO3+IPI1) of patients. Three patients achieved a partial 
      response (NIVO3, n = 1; NIVO3+IPI1, n = 2) and 8 had stable disease for >/=12 weeks 
      (NIVO3, n = 2; NIVO1+IPI3, n = 2; NIVO3+IPI1, n = 4 [Response Assessment in 
      Neuro-Oncology criteria]). Most patients (68%) had tumor-cell programmed death 
      ligand-1 expression >/=1%. Immune-mediated effects mimicking radiographic 
      progression occurred in 2 patients. CONCLUSIONS: Nivolumab monotherapy was better 
      tolerated than nivolumab + ipilimumab; the tolerability of the combination was 
      influenced by ipilimumab dose. These safety and exploratory findings merit 
      further investigation of immunotherapies in glioblastoma.
FAU - Omuro, Antonio
AU  - Omuro A
AD  - Memorial Sloan Kettering Cancer Center, New York, New York.
FAU - Vlahovic, Gordana
AU  - Vlahovic G
AD  - Duke University Medical Center, Durham, North Carolina.
FAU - Lim, Michael
AU  - Lim M
AD  - The Johns Hopkins Hospital, Baltimore, Maryland.
FAU - Sahebjam, Solmaz
AU  - Sahebjam S
AD  - Moffitt Cancer Center, University of South Florida, Tampa, Florida.
FAU - Baehring, Joachim
AU  - Baehring J
AD  - Yale School of Medicine, New Haven, Connecticut.
FAU - Cloughesy, Timothy
AU  - Cloughesy T
AD  - University of California Los Angeles, Los Angeles, California.
FAU - Voloschin, Alfredo
AU  - Voloschin A
AD  - Emory University School of Medicine, Atlanta, Georgia.
FAU - Ramkissoon, Shakti H
AU  - Ramkissoon SH
AD  - Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
FAU - Ligon, Keith L
AU  - Ligon KL
AD  - Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
FAU - Latek, Robert
AU  - Latek R
AD  - Bristol-Myers Squibb, Princeton, New Jersey.
FAU - Zwirtes, Ricardo
AU  - Zwirtes R
AD  - Bristol-Myers Squibb, Princeton, New Jersey.
FAU - Strauss, Lewis
AU  - Strauss L
AD  - Bristol-Myers Squibb, Princeton, New Jersey.
FAU - Paliwal, Prashni
AU  - Paliwal P
AD  - Bristol-Myers Squibb, Princeton, New Jersey.
FAU - Harbison, Christopher T
AU  - Harbison CT
AD  - Bristol-Myers Squibb, Princeton, New Jersey.
FAU - Reardon, David A
AU  - Reardon DA
AD  - Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
FAU - Sampson, John H
AU  - Sampson JH
AD  - Duke University Medical Center, Durham, North Carolina.
LA  - eng
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - P50 CA211015/CA/NCI NIH HHS/United States
GR  - R01 NS116888/NS/NINDS NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - 0 (Ipilimumab)
RN  - 31YO63LBSN (Nivolumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Brain Neoplasms/*drug therapy/pathology
MH  - Cohort Studies
MH  - Female
MH  - Follow-Up Studies
MH  - Glioblastoma/*drug therapy/pathology
MH  - Humans
MH  - Ipilimumab/administration & dosage
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy/pathology
MH  - Nivolumab/administration & dosage
MH  - Prognosis
PMC - PMC5892140
EDAT- 2017/11/07 06:00
MHDA- 2019/01/17 06:00
PMCR- 2019/04/09
CRDT- 2017/11/07 06:00
PHST- 2017/11/07 06:00 [pubmed]
PHST- 2019/01/17 06:00 [medline]
PHST- 2017/11/07 06:00 [entrez]
PHST- 2019/04/09 00:00 [pmc-release]
AID - 4587521 [pii]
AID - nox208 [pii]
AID - 10.1093/neuonc/nox208 [doi]
PST - ppublish
SO  - Neuro Oncol. 2018 Apr 9;20(5):674-686. doi: 10.1093/neuonc/nox208.