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Neuro Oncol. 2018 Apr 9;20(5):674-686. doi: 10.1093/neuonc/nox208.

Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143.

Author information

1
Memorial Sloan Kettering Cancer Center, New York, New York.
2
Duke University Medical Center, Durham, North Carolina.
3
The Johns Hopkins Hospital, Baltimore, Maryland.
4
Moffitt Cancer Center, University of South Florida, Tampa, Florida.
5
Yale School of Medicine, New Haven, Connecticut.
6
University of California Los Angeles, Los Angeles, California.
7
Emory University School of Medicine, Atlanta, Georgia.
8
Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
9
Bristol-Myers Squibb, Princeton, New Jersey.

Abstract

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.

PMID:
29106665
PMCID:
PMC5892140
DOI:
10.1093/neuonc/nox208
[Indexed for MEDLINE]
Free PMC Article

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