LBA15 - Randomized multicenter phase II trial of irinotecan and bevacizumab as neo-adjuvant and adjuvant to temozolomide-based chemoradiation versus chemora...

Date 01 October 2012
Event ESMO Congress 2012
Session CNS tumors
Topics Anti-Cancer Agents & Biologic Therapy
Central Nervous System Malignancies
Presenter Bruno Chauffert
Authors B. Chauffert1, L. Feuvret2, F. Bonnetain3, L. Taillandier4, D. Frappaz5, J. Honnorat6, M. Fabbro7, M. Frenay8, X. Durando9, I. Tennevet10, J.S. Guillamo11, H. Tailla12, R. Schott13, F. Ghiringhelli14, C. Campello15, N. Tubiana-Mathieu16, C. Dalban17, J. Skrzypski3, O. Chinot18
  • 1University Hospital, 80054 - AMIENS CEDEX/FR
  • 2Radiotherapy, CHU PITIE SALPETRIERE, PARIS/FR
  • 3Biostatistic And Epidemiological Unit(ea 4184), Centre Georges François Leclerc, 21000 - Dijon/FR
  • 4Neurology, CHU Nancy, 54000 - NANCY/FR
  • 5Oncology, CLCC LEON BERARD, 69000 - LYON/FR
  • 6Neurologie, CHU LYON, 69000 - LYON/FR
  • 7Médecine B2, CLCC Val d'Aurelle, MONTPELLIER/FR
  • 8Oncology, CLCC Lacassagne, NICE/FR
  • 9Oncology, CLCC Jean Perrin, CLERMONT FERRAND/FR
  • 10Oncology, CLCC H BECQUEREL, ROUEN/FR
  • 11Neurology, CHU CAEN, CAEN/FR
  • 12Neurology, HIA Val de Grace, PARIS/FR
  • 13Oncology, CLCC Paul Strauss, Strasbourg/FR
  • 14Oncology, CLCC GF Leclerc, Dijon/FR
  • 15Neurorolgy, CHU NIMES, NIMES/FR
  • 16Medical Oncology, Hopital Dupuytren-CHU Limoges, 87042 - Limoges CEDEX /FR
  • 17Department Of Biostatistics And Epidemiology (ea4184), Centre Georges François Leclerc, 21079 - Dijon/FR
  • 18Neurooncology, AP-HM Timone, Marseille/FR

 

Abstract

Randomized multicenter phase II trial of irinotecan and bevacizumab as neo-adjuvant and adjuvant to temozolomide-based chemoradiation versus chemoradiation for unresectable glioblastoma (definitive results of the TEMAVIR ANOCEF study).

Background.

The prognosis of unresectable glioblastoma (GBM) remains poor despite temozolomide (TMZ)- based chemoradiation. Activity of bevacizumab/irinotecan has been reported in recurrent GBM (Vredenburgh, 2007). We evaluate irinotecan (IRI) and bevacizumab (BVZ) as neo-adjuvant and adjuvant to TMZ-based chemoradiation for unresectable glioblastoma.

Method:

Pts with de novo unresectable GBM, aged 18-70, and KPS > 50, and RPA class 5 were eligible. Experimental arm (A) consisted of neo-adjuvant BVZ 10 mg/kg and IRI 125 mg/m2, every 2 wk for 4 cycles before radiotherapy (60 Gy in 30 fractions) with concurrent TMZ 75 mg/m2/day and BVZ every 2 wk. Adjuvant BVZ and IRI were given every 2 wk for 6 months. The control arm (B) consisted of concomitant TMZ, 75 mg/m2/d during radiotherapy and 150-200 mg/m2 for 5 d every 28 d for 6 months. Cross over were allowed at progression. The inclusion of 60 pts/arm was planned using Fleming’s 2 steps design aiming at an increase of PFS at 6 month (PFS6) from 50 % to 66 %, with unilateral alpha 5% and 80% power. Final analysis, including overall survival (OS), was performed 16 months after the end of inclusion.

Results:

Patients (120) were included from April 2009 to January 2011. Clinical factors were well balanced between arms. Treatment-related serious adverse events were brain haemorrhages (3; 3 fatal), biliary or digestive perforation/infection (3, 1 fatal), thrombo-embolism (4, 0 fatal) in Arm A, and biliary or digestive perforation/infection (2, 0 fatal), pulmonary infection (1, no fatal), thrombo-embolism (2, 0 fatal), thrombo- and/or neutrepenia (4, 0 fatal) in arm B. PFS at 6 and 12 months appears to be longer in arm A, but OS was similar in both arms (table).

ARM

(patients)

PFS 6

%

[IC95, %]

PFS 12

%

[IC95, %]

OS 6

%

[IC95, %]

OS 12

%

[IC95, %]

A (60)

65

[51-75]

31

[20-43]

75

[62-84]

48

[34-60]

B (60)

41

[29 -53]

18

[9-28]

72

[59-82]

50

[36-62]

Conclusion:

Despite a trend to a better PFS at 6 and 12 month in the experimental arm, overall survival was not different between arms.