A phase II, randomized, study of weekly APG101+reirradiation versus reirradiation in progressive glioblastoma
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A phase II, randomized, study of weekly APG101+reirradiation versus reirradiation in progressive glioblastoma. / Wick, Wolfgang; Fricke, Harald; Junge, Klaus; Kobyakov, Grigory; Martens, Tobias; Heese, Oliver; Wiestler, Benedikt; Schliesser, Maximilian G; Pichler, Josef; Vetlova, Elena; Harting, Inga; Debus, Jürgen; Hartmann, Christian; Kunz, Claudia; Platten, Michael; Bendszus, Martin; Combs, Stephanie E.
In: CLIN CANCER RES, Vol. 20, No. 24, 15.12.2014, p. 6304-13.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - A phase II, randomized, study of weekly APG101+reirradiation versus reirradiation in progressive glioblastoma
AU - Wick, Wolfgang
AU - Fricke, Harald
AU - Junge, Klaus
AU - Kobyakov, Grigory
AU - Martens, Tobias
AU - Heese, Oliver
AU - Wiestler, Benedikt
AU - Schliesser, Maximilian G
AU - Pichler, Josef
AU - Vetlova, Elena
AU - Harting, Inga
AU - Debus, Jürgen
AU - Hartmann, Christian
AU - Kunz, Claudia
AU - Platten, Michael
AU - Bendszus, Martin
AU - Combs, Stephanie E
N1 - ©2014 American Association for Cancer Research.
PY - 2014/12/15
Y1 - 2014/12/15
N2 - PURPOSE: Preclinical data indicate anti-invasive activity of APG101, a CD95 ligand (CD95L)-binding fusion protein, in glioblastoma.EXPERIMENTAL DESIGN: Patients (N = 91) with glioblastoma at first or second progression were randomized 1:2 between second radiotherapy (rRT; 36 Gy; five times 2 Gy per week) or rRT+APG101 (400 mg weekly i.v.). Patient characteristics [N = 84 (26 patients rRT, 58 patients rRT+APG101)] were balanced.RESULTS: Progression-free survival at 6 months (PFS-6) rates were 3.8% [95% confidence interval (CI), 0.1-19.6] for rRT and 20.7% (95% CI, 11.2-33.4) for rRT+APG101 (P = 0.048). Median PFS was 2.5 (95% CI, 2.3-3.8) months and 4.5 (95% CI, 3.7-5.4) months with a hazard ratio (HR) of 0.49 (95% CI, 0.27-0.88; P = 0.0162) adjusted for tumor size. Cox regression analysis adjusted for tumor size revealed a HR of 0.60 (95% CI, 0.36-1.01; P = 0.0559) for rRT+APG101 for death of any cause. Lower methylation levels at CpG2 in the CD95L promoter in the tumor conferred a stronger risk reduction (HR, 0.19; 95% CI, 0.06-0.58) for treatment with APG101, suggesting a potential biomarker.CONCLUSIONS: CD95 pathway inhibition in combination with rRT is an innovative concept with clinical efficacy. It warrants further clinical development. CD95L promoter methylation in the tumor may be developed as a biomarker.
AB - PURPOSE: Preclinical data indicate anti-invasive activity of APG101, a CD95 ligand (CD95L)-binding fusion protein, in glioblastoma.EXPERIMENTAL DESIGN: Patients (N = 91) with glioblastoma at first or second progression were randomized 1:2 between second radiotherapy (rRT; 36 Gy; five times 2 Gy per week) or rRT+APG101 (400 mg weekly i.v.). Patient characteristics [N = 84 (26 patients rRT, 58 patients rRT+APG101)] were balanced.RESULTS: Progression-free survival at 6 months (PFS-6) rates were 3.8% [95% confidence interval (CI), 0.1-19.6] for rRT and 20.7% (95% CI, 11.2-33.4) for rRT+APG101 (P = 0.048). Median PFS was 2.5 (95% CI, 2.3-3.8) months and 4.5 (95% CI, 3.7-5.4) months with a hazard ratio (HR) of 0.49 (95% CI, 0.27-0.88; P = 0.0162) adjusted for tumor size. Cox regression analysis adjusted for tumor size revealed a HR of 0.60 (95% CI, 0.36-1.01; P = 0.0559) for rRT+APG101 for death of any cause. Lower methylation levels at CpG2 in the CD95L promoter in the tumor conferred a stronger risk reduction (HR, 0.19; 95% CI, 0.06-0.58) for treatment with APG101, suggesting a potential biomarker.CONCLUSIONS: CD95 pathway inhibition in combination with rRT is an innovative concept with clinical efficacy. It warrants further clinical development. CD95L promoter methylation in the tumor may be developed as a biomarker.
KW - Adult
KW - Aged
KW - Antigens, CD95
KW - Antineoplastic Agents
KW - Biomarkers
KW - Combined Modality Therapy
KW - Drug Administration Schedule
KW - Female
KW - Glioblastoma
KW - Humans
KW - Immunoglobulin G
KW - Male
KW - Middle Aged
KW - Prognosis
KW - Quality of Life
KW - Recombinant Fusion Proteins
KW - Treatment Outcome
KW - Tumor Burden
KW - Young Adult
U2 - 10.1158/1078-0432.CCR-14-0951-T
DO - 10.1158/1078-0432.CCR-14-0951-T
M3 - SCORING: Journal article
C2 - 25338498
VL - 20
SP - 6304
EP - 6313
JO - CLIN CANCER RES
JF - CLIN CANCER RES
SN - 1078-0432
IS - 24
ER -