title: NRG oncology RTOG 0625: a randomized phase II trial of bevacizumab with either irinotecan or dose-dense temozolomide in recurrent glioblastoma.
abstract: Angiogenesis, a hallmark of glioblastoma, can potentially be targeted by inhibiting the VEGF pathway using bevacizumab, a humanized monoclonal antibody against VEGF-A. This study was designed to determine the efficacy and safety of these regimens in the cooperative group setting. Eligibility included age ≥18, recurrent or progressive GBM after standard chemoradiation. Treatment was intravenous bevacizumab 10 mg/kg and either irinotecan (CPT) 125 mg/m2every 2 weeks or temozolomide (TMZ) 75-100 mg/m2day 1-21 of 28 day cycle. Accrual goal was 57 eligible patients per arm. Primary endpoint was 6 month progression-free survival (6-m PFS); a predetermined rate of ≥35 % to declare efficacy. 60 eligible patients were enrolled on TMZ arm and 57 patients on CPT arm. Median age was 56, median KPS was 80. For TMZ arm, the 6-m-PFS rate was 39 % (23/59); for the CPT arm, the 6-m-PFS rate was 38.6 % (22/57). Objective responses: TMZ arm had 2 (3 %) CR, 9 (16 %) PR; CPT arm had 2 (4 %) CR, 13 (24 %) PR. Overall there was moderate toxicity: TMZ arm with 33 (55 %) grade 3, 11 (18 %) grade 4, and 1 (2 %) grade 5 (fatal) toxicities; CPT arm had 22 (39 %) grade 3, 7 (12 %) grade 4, and 3 (5 %) grade 5 toxicities. The 6-m-PFS surpassed the predetermined efficacy threshold for both arms, corroborating the efficacy of bevacizumab and CPT and confirming activity for bevacizumab and protracted TMZ for recurrent/progressive GBM, even after prior temozolomide exposure. Toxicities were within anticipated frequencies with a moderately high rate of venous thrombosis, moderate hypertension and one intracranial hemorrhage.
authors: Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bloch Bldg. 82, Rm. 235, 9030 Old George town Road, Bethesda, MD, 20892, USA. mark.gilbert@nih.gov.
authors: Mark R
authors: MR
authors: Gilbert
authors: NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA.
authors: Stephanie L
authors: SL
authors: Pugh
authors: University of Toronto, Toronto, Canada.
authors: Ken
authors: K
authors: Aldape
authors: Massachusetts General Hospital, Boston, MA, USA.
authors: A Gregory
authors: AG
authors: Sorensen
authors: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
authors: Tom
authors: T
authors: Mikkelsen
authors: University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Marta
authors: M
authors: Penas-Prado
authors: Tel-Aviv Medical Center, Tel-Aviv, Israel.
authors: Felix
authors: F
authors: Bokstein
authors: University of Maryland, Baltimore, MD, USA.
authors: Young
authors: Y
authors: Kwok
authors: Intermountain Medical Center, Murray, UT, USA.
authors: R Jeffrey
authors: RJ
authors: Lee
authors: University of Maryland, Baltimore, MD, USA.
authors: Minesh
authors: M
authors: Mehta
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000074322:Antineoplastic Agents, Immunological; D000068258:Bevacizumab / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D003404:Creatinine / Q000652:urine; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000077204:Temozolomide; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000074322:Antineoplastic Agents, Immunological; D000068258:Bevacizumab; D003606:Dacarbazine; D003404:Creatinine; D000077204:Temozolomide
keywords: Anti-angiogenic treatment; Combination therapy; Glioblastoma; Randomized trial