Veliparib in combination with whole-brain radiation therapy for patients with brain metastases from non-small cell lung cancer: results of a randomized, global, placebo-controlled study.

Autor: Chabot P; Hôpital Maisonneuve-Rosemont, Montreal, QC, Canada., Hsia TC; China Medical University Hospital, China Medical University, Taichung, Taiwan, People's Republic of China., Ryu JS; Inha University Hospital, Jung-Gu, Incheon, South Korea., Gorbunova V; N.N. Blokhin Russian Cancer Research Center, Moscow, Russia., Belda-Iniesta C; Centro Integral Oncológico Clara Campal HM Sanchinarro, Madrid, Spain., Ball D; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Kio E; IU Health Goshen Center for Cancer Care, Goshen, IN, USA., Mehta M; University of Maryland, College Park, MD, USA., Papp K; AbbVie Inc., Chicago, IL, USA., Qin Q; AbbVie Inc., Chicago, IL, USA., Qian J; AbbVie Inc., Chicago, IL, USA., Holen KD; AbbVie Inc., Chicago, IL, USA., Giranda V; AbbVie Inc., Chicago, IL, USA., Suh JH; Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA. suhj@ccf.org.
Jazyk: angličtina
Zdroj: Journal of neuro-oncology [J Neurooncol] 2017 Jan; Vol. 131 (1), pp. 105-115. Date of Electronic Publication: 2016 Sep 21.
DOI: 10.1007/s11060-016-2275-x
Abstrakt: Veliparib is a potent, orally bioavailable, poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor that crosses the blood-brain barrier and has been shown to potentiate the effects of radiation in preclinical and early clinical studies. This phase 2, randomized, global study evaluated the efficacy and safety of veliparib in combination with whole-brain radiation therapy (WBRT) in patients with brain metastases from non-small cell lung cancer (NSCLC). Three-hundred and seven patients with brain metastases from NSCLC were randomized 1:1:1 to WBRT (30 Gy in 10 fractions) plus 50 mg veliparib twice daily (BID; n = 103), 200 mg veliparib BID (n = 102), or placebo BID (n = 102). Treatment began within 28 days of diagnosis. Tumor response and safety were assessed; the primary endpoint was overall survival (OS). Patients who received ≥1 dose of treatment were included in the safety analysis. All randomized patients were included in the efficacy endpoint analyses. Patient characteristics were well balanced between treatment arms. Median OS was 185 days for patients treated with WBRT plus placebo and 209 days for WBRT plus veliparib (50 or 200 mg). No statistically significant differences in OS, intracranial response rate, and time to clinical or radiographic progression between any of the treatment arms were noted. No differences were observed in adverse events (all grades) across treatment arms; nausea, fatigue, alopecia, and headache were the most commonly reported. No new safety signals were identified for veliparib. A significant unmet need for therapies that improve the outcomes of patients with brain metastases from NSCLC remains.
Competing Interests: PC, T-CH, J-SR, VG, CB, and EK have no conflict of interest to disclose. DB has participated as an investigator for AbbVie, his institution was reimbursed by AbbVie for expenses incurred, he received research funding from AbbVie and has participated on advisory boards for Boehringer Ingelheim, AstraZeneca, and Lilly Oncology. MM has received consultant honoraria from BMS, Cavion, Celldex, Elekta, Novartis, Novocure, and has served on the Board of Directors of Pharmacyclics, with stock options, and has institutional research funding from Novocure and Cellectar. JHS has received consultant honoraria and has received research funding from Varian Medical Systems and has had travel and lodging covered by Elekta. KP, QQ, JQ, KDH, and VG are AbbVie employees and may own stock. Ethical approval This study was approved by an Independent Ethics Committee/Independent Review Board before initiation and was performed in accordance with the 1964 Declaration of Helsinki and its later amendments. Informed consent All patients provided written informed consent before their participation.
Databáze: MEDLINE
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