Annals of Oncology 25 (Supplement 4): iv137–iv145, 2014
doi:10.1093/annonc/mdu330.1
CNS tumours
414O
RANDOMIZED PHASE II TRIAL AVAREG (ML25739) WITH
BEVACIZUMAB (BEV) OR FOTEMUSTINE (FTM) IN RECURRENT
GBM: FINAL RESULTS FROM THE RANDOMIZED PHASE II
TRIAL
Conclusions: BEV in recurrent GBM showed survival rates superimposable with FTM.
Disclosure: V. Zagonel: Roche – Speaker; M. Reni: Genentech - Advisory board;
G. Rosti: Roche - Speaker A. Galli: Roche – employee; S. Doria: Roche – employee; All
other authors have declared no conflicts of interest.
Aim: The treatment of recurrent glioblastoma (GBM) remains an open issue and the
role of BEV has been largely debated since only few data compared this agent with the
standard agents.
Methods: A multicenter, open label, randomized (2:1), non-comparative phase II study
(EudraCT 2011-001363-46; AVAREG - ML25739) with BEV 10 mg/m2 iv every 2
weeks or FTM 75 mg/m2 iv day 1-8-15 followed, after a 35 days interval, by FTM 100
mg/m2 every 3 weeks was conducted. Primary endpoint was overall survival at 6
months (OS6). Stratification factors were age (<55 years [yrs] or >55 yrs) and resection
for recurrent disease (yes vs no).
Results: 91 patients ( pts) with recurrent GBM were enrolled among 10 Italian centers
between 11/2011 and 9/2012. Median age was 57 yrs (range: 28-78), ECOG PS was 0/1/
2 in 42/35/14 pts. All pts received RT/TMZ accordingly with EORTC 26981-22981/
NCIC CE3. Time from diagnosis to 1st recurrence was 331 days in the BEV arm and
460 days in the FTM arm. At the time of recurrence, 21 pts (23.1%) underwent
re-resection before the inclusion into the study (13/8 pts in BEV/FTM arms,
respectively). Fifty-nine pts were enrolled in the BEV arm and 32 pts in the FTM arm.
OS6 was 62.1% (95%CI: 48.4 - 74.5) and 73.3% (95%CI: 54.1 - 87.7), OS9 was 37.9%
(95%CI: 25.5–51.6) and 46.7% (95%CI 28.3–65.7) in the BEV and FTM arms,
respectively. Median OS was 7.3 months (95%CI: 5.8 - 9.2) in the BEV arm and 8.7
months (95%CI: 6.3-15.4) in the FTM arm. In the BEV arm, OS6 and OS9 were 77.8%
(95%CI: 57.7–91.4) and 59.3% (95%CI: 38.8 - 77.6) in pts ≤55 yrs, and were 48.4%
(95%CI: 30.1 - 66.9) and 19.3% (95%CI: 7.4 - 37.5) in pts >55 yrs. HR for OS in BEV
group for pts >55 yrs compared with pts ≤55 yrs was 2.0 (95%CI: 1.0-4.1, p = 0.05).
Table: 414O
G 3-4- toxicity
Neutropenia
Thrombocytopenia
Intestinal perforation
Cerebral ischaemia/haemorrage
Pulmonary embolism
Acute myocardial infarction
BEV
1 (1.7%)
0
2 (3.4%)
2 (3.4%)
1 (1.7%)
1 (1.7%)
FTM
4 (12.5%)
7 (21.9%)
0
0
0
0
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: journals.permissions@oup.com.
abstracts
A. Brandes1, G. Finocchiaro2, V. Zagonel3, A. Fabi4, C. Caserta5, M. Reni6,
M. Clavarezza7, E. Maiello8, G. Carteni9, G. Rosti10, M. Eoli2, G. Lombardi11,
M. Monteforte12, R. Agati13, V. Eusebi14, A. Galli15, S. Doria15, E. Franceschi16
1
Dept. Medical Oncology, Bellaria-Maggiore Hospital, Azienda USL - IRCCS
Institute of Neurological Sciences, Bologna, ITALY
2
Molecular Neuro-oncology, IRCCS Istituto Neurologico Carlo Besta, Milan, ITALY
3
Department of Oncology, IOV-IRCCS, Padua, ITALY
4
Divisione Di Oncologia Medica A, Istituto Nazionali Tumori Regina Elena, Rome,
ITALY
5
Oncology Dept., Azienda Ospedaliera Santa Maria, Terni, ITALY
6
Oncologia, IRCCS San Raffaele, Milan, ITALY
7
Sc Oncologia Medica, EO Galliera, Genova, ITALY
8
Oncology Dept., IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo,
ITALY
9
Onco-hematology, Azienda Ospedaliera Cardarelli, Naples, ITALY
10
UOC Oncologia Medica, Ospedale Regionale Ca’ Foncello, Treviso, ITALY
11
U.O. Oncologia Medica, Istituto Oncologico Veneto IRCCS, Padua, ITALY
12
On Pharmaceutical Industry Service - Opis Srl, On Pharmaceutical Industry
Service - OPIS srl, Desio, ITALY
13
Neuroradiology Department, Bellaria-Maggiore Hospital, Azienda USL, Bologna,
ITALY
14
Dipartimento Di Oncologia, Sezione Di Anatomia Patologica, Ospedale Bellaria,
Bologna, ITALY
15
Roche Italy, Roche Italy, Monza, ITALY
16
Dept. Medical Oncology, Ospedale Bellaria, Bologna, ITALY