OS09.3.A FINAL RESULTS OF THE MGMT UNMETHYLATED ARM OF PARADIGM-2: A PHASE I STUDY OF OLAPARIB AND RADIOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA (GBM)

Abstract BACKGROUND The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib has radio and chemosensitizing effects in preclinical models and penetrates GBM in patients at radiosensitizing concentrations. PARP inhibitors sensitize proliferating cells to temozolomide (TMZ) but exacerbate haematologi...

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Published in:Neuro-oncology (Charlottesville, Va.) Va.), 2023-09, Vol.25 (Supplement_2), p.ii20-ii21
Main Authors: Derby, S J, Sweeting, L, Shad, S, Paterson, L, Stobo, J, Nowicki, S, Williamson, A, James, A, Short, S C, McBain, C, Herbert, C, Powell, J, Kelly, C, Chalmers, A J
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Language:English
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Summary:Abstract BACKGROUND The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib has radio and chemosensitizing effects in preclinical models and penetrates GBM in patients at radiosensitizing concentrations. PARP inhibitors sensitize proliferating cells to temozolomide (TMZ) but exacerbate haematological toxicity. Patients with MGMT unmethylated tumours do not benefit from TMZ so it can be withheld, enabling continuous olaparib dosing with radiotherapy (RT). Patients with MGMT methylated tumours benefit from TMZ so olaparib must be combined with chemoradiation (CRT) in an intermittent, low-dose manner. PARADIGM-2 is a clinical trial comprising two parallel phase I studies of olaparib/RT or olaparib/RT/TMZ in newly diagnosed GBM patients stratified by MGMT status. MATERIAL AND METHODS GBM patients aged
ISSN:1522-8517
1523-5866
DOI:10.1093/neuonc/noad137.060