414O - Randomized phase II trial AVAREG (ML25739) with bevacizumab (BEV) or fotemustine (FTM) in recurrent GBM: Final results from the randomized phase II...

Date 27 September 2014
Event ESMO 2014
Session CNS tumours
Topics Anti-Cancer Agents & Biologic Therapy
Central Nervous System Malignancies
Presenter Alba Brandes
Citation Annals of Oncology (2014) 25 (suppl_4): iv137-iv145. 10.1093/annonc/mdu330
Authors 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
  • 1Dept. Medical Oncology, Bellaria-Maggiore Hospital, Azienda USL - IRCCS Institute of Neurological Sciences, 40139 - Bologna/IT
  • 2Molecular Neuro-oncology, IRCCS Istituto Neurologico Carlo Besta, 20133 - Milano/IT
  • 3Department Of Oncology, IOV-IRCCS, 35128 - Padova/IT
  • 4Divisione Di Oncologia Medica A, Istituto Nazionali Tumori Regina Elena, 00186 - Rome/IT
  • 5Oncology Dept., Azienda Ospedaliera Santa Maria, 05100 - Terni/IT
  • 6Oncologia, IRCCS San Raffaele, 20132 - Milano/IT
  • 7Sc Oncologia Medica, EO Galliera,, 16128 - Genova/IT
  • 8Oncology Dept., IRCCS Casa Sollievo della Sofferenza, 71013 - San Giovanni Rotondo/IT
  • 9Onco-hematology, Azienda Ospedaliera Cardarelli, 80131 - Napoli/IT
  • 10Uoc Oncologia Medica, Ospedale Regionale Ca' Foncello, 31100 - Treviso/IT
  • 11U.o.oncologia Medica, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 12On Pharmaceutical Industry Service - Opis Srl, On Pharmaceutical Industry Service - OPIS srl, 20832 - Desio/IT
  • 13Neuroradiology Department, Bellaria-Maggiore Hospital, Azienda USL, Bologna/IT
  • 14Dipartimento Di Oncologia, Sezione Di Anatomia Patologica, Ospedale Bellaria, Bologna/IT
  • 15Roche Italy, Roche Italy, 20052 - Monza/IT
  • 16Dept. Medical Oncology, Ospedale Bellaria, 40139 - Bologna/IT

 

Abstract

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).

G 3-4- toxicity BEV FTM
Neutropenia 1 (1.7%) 4 (12.5%)
Thrombocytopenia 0 7 (21.9%)
Intestinal perforation 2 (3.4%) 0
Cerebral ischaemia/haemorrage 2 (3.4%) 0
Pulmonary embolism 1 (1.7%) 0
Acute myocardial infarction 1 (1.7%) 0

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.