@article{a819ffe0f21d4247a58dd4393237331b,
title = "A randomized phase I/II study of ABT-888 in combination with temozolomide in recurrent temozolomide resistant glioblastoma: An NRG oncology RTOG group study",
abstract = "This study tested the hypothesis that ABT-888 (velparib), a poly (ADP-ribose) polymerase (PARP) inhibitor, can modulate temozolomide (TMZ) resistance in recurrent TMZ refractory glioblastoma patients. The combination regimen (TMZ/ABT-888) was tested using two randomized schedules (5 vs. 21 days), with 6-month progression free survival (PFS6) as the primary endpoint. The maximum tolerated dose (MTD) for TMZ using the 21 day of 28 TMZ schedule, in concert with 40 mg BID ABT-888 was determined in a phase I portion of this study, and previously reported to be 75 mg/m2(arm1). The MTD for ABT-888 (40 mg BID) and the 5 of 28 day TMZ (150-200 mg/m2) schedule was known from prior trials (arm2). Two cohorts were studied: bevacizumab (BEV) na{\"i}ve (n = 151), and BEV refractory (n = 74). Overall ten patients were ineligible. The incidence rate of grade 3/4 myelosuppression over all was 20.0%. For the BEV refractory cohort, the PFS 6 was 4.4%; for the BEV na{\"i}ve cohort, PFS6 was 17%. Overall survival was similar for both arms in both the BEV na{\"i}ve [median survival time (MST) 10.3 M; 95% CI 8.4-12] and BEV refractory cohort (MST 4.7 M; 95%CI 3.5-5.6). The median PFS was essentially the same for both arms and both cohorts at ~2.0 M (95% CI 1.9-2.1).",
keywords = "ABT-888, Glioblastoma, Temozolomide, Velparib",
author = "Robins, {H. Ian} and Peixin Zhang and Gilbert, {Mark R.} and Arnab Chakravarti and {de Groot}, {John F.} and Grimm, {Sean A.} and Fen Wang and Lieberman, {Frank S.} and Andra Krauze and Trotti, {Andy M.} and Nimish Mohile and Kee, {Andrew Y.J.} and Howard Colman and Robert Cavaliere and Santosh Kesari and Chmura, {Steven J.} and Minesh Mehta",
note = "Funding Information: H. Ian Robins reports grants and personal fees from Novocure, personal fees from AbbVie, outside the submitted work. Mark R Gilbert reports personal fees and non-financial support from Merck, personal fees from Genentech Roche, personal fees from AbbVie, personal fees from Wellcome Trust, and personal fees from Foundation Medicine, outside the submitted work. Frank S Lieberman reports grants and personal fees from Roche (Genentech), grants from Novacure, grants from Celldex, and grants from Stemline, outside the submitted work. Nimish Mohile reports personal fees from Novocure, personal fees from AbbVie, outside the submitted work. Howard Colman reports personal fees from Hoffman La Roche, personal fees from Genentech, personal fees from Sigma Tau, personal fees from Proximagen/Upsher Smith, personal fees from Foundation Medicine, personal fees from Merck, outside the submitted work. Santosh Kesari reports personal fees from Novocure, personal fees from Sigma Tau, grants from Celldex, grants from Tocagen, grants from NWBT, grants from Novartis, outside the submitted work. Minesh Mehta reports personal fees from AbbVie, personal fees from BMS, personal fees from Celldex, grants and personal fees from Novelos, personal fees from Phillips, personal fees from Roche, personal fees from Elekta, personal fees from Novartis, personal fees from Cavion, grants and personal fees from Novocure, personal fees from Pharmacyclics, outside the submitted work. Funding Information: This project was supported by Grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, and UG1CA189867 from the National Cancer Institute (NCI) and AbbVie. Publisher Copyright: {\textcopyright} Springer Science+Business Media New York 2015.",
year = "2016",
month = jan,
doi = "10.1007/s11060-015-1966-z",
language = "English (US)",
volume = "126",
pages = "309--316",
journal = "Journal of neuro-oncology",
issn = "0167-594X",
publisher = "Kluwer Academic Publishers",
number = "2",
}