title: 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.
abstract: 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.
authors.affiliation: Hôpital Maisonneuve-Rosemont, Montreal, QC, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Chabot
authors.affiliation: China Medical University Hospital, China Medical University, Taichung, Taiwan, People's Republic of China.
authors.forename: Te-Chun
authors.initials: TC
authors.lastname: Hsia
authors.affiliation: Inha University Hospital, Jung-Gu, Incheon, South Korea.
authors.forename: Jeong-Seon
authors.initials: JS
authors.lastname: Ryu
authors.affiliation: N.N. Blokhin Russian Cancer Research Center, Moscow, Russia.
authors.forename: Vera
authors.initials: V
authors.lastname: Gorbunova
authors.affiliation: Centro Integral Oncológico Clara Campal HM Sanchinarro, Madrid, Spain.
authors.forename: Cristobal
authors.initials: C
authors.lastname: Belda-Iniesta
authors.affiliation: Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ball
authors.affiliation: IU Health Goshen Center for Cancer Care, Goshen, IN, USA.
authors.forename: Ebenezer
authors.initials: E
authors.lastname: Kio
authors.affiliation: University of Maryland, College Park, MD, USA.
authors.forename: Minesh
authors.initials: M
authors.lastname: Mehta
authors.affiliation: AbbVie Inc., Chicago, IL, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Papp
authors.affiliation: AbbVie Inc., Chicago, IL, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Qin
authors.affiliation: AbbVie Inc., Chicago, IL, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Qian
authors.affiliation: AbbVie Inc., Chicago, IL, USA.
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Holen
authors.affiliation: AbbVie Inc., Chicago, IL, USA.
authors.forename: Vince
authors.initials: V
authors.lastname: Giranda
authors.affiliation: Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA. suhj@ccf.org.
authors.forename: John H
authors.initials: JH
authors.lastname: Suh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D016371:Cranial Irradiation / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; C521013:veliparib
keywords: Brain metastases; Non-small cell lung cancer; PARP inhibitor; Randomized clinical trial; Veliparib; Whole-brain radiation therapy