Terapie antiangiogenetiche: revisione e gestione degli eventi avversi Lucia Del Mastro SS Sviluppo Terapie Innovative Modena- 18 Novembre 2011 IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro
Fatal adverse event – Death caused in all likelihhod by a drug -> major cause of fatality in USA – 0.3% in prespective studies – 4.6% of all hospital fatality
CAIRO study tested the optimal use of well- established cyctotoxic (capecitabine, irinoteca, oxaliplatin) 820 enrolled patients – 112 deaths (14%) occurring within 30 days of last administration of study drug 72 (9%) deaths caused by PD 40 (5%) deaths without PD
Relationship between cause of death and study drugs changed in 65% of patients -> underestimation by local investigators of the relation between the administration of study drugs and death
Beva vs contl AVF2119g:0 events E2100: 0.5% vs 0.3% Avado: 0.8% vs 1.7% RIBBON1: 1.7% vs 2.7% Overall: OR: (95% CI ; p=0.183
ATEs: Beva: 0.93% Cntl: 0.56 OR: 1.49 ( ) P=0.3 VTEs: Beva: 2.6% Cntl: 2.6% OR: 1.06 ( ) P=0.78
Beva: 0.51% Cntl: 0.21% OR: 1.84 P=0.327 Beva: 4.9% Cntl: 2.8% OR: 1.45 P=0.052
Beva: 9.7% Cntl: 0.64% OR: ( ) P=0.001 OR: P<0.0001
Beva: 1.31% Cntl: 0.28% OR: 4.07 P=0.006
Beva: 1.73% Cntl: 0.78% OR: 2.25 ( ) P=0.017
Beva: 1.6% Cntl: 0.4% RR 4.74 ( ) P=0.001
Bevacizumab and osteonecrosis of the jaw Hypothesis: because healing after mucosal trauma requires re-vascularization, the combination of Beva and a biphosphonate could affect the incidence, the time to development of ONJ and/or the response to dental therapy.
Bevacizumab and osteonecrosis of the jaw ONJ incidence Biphosphonate alone1-6% 1 Bevacizumab alone0.3-1% 2,3 Bevacizumab + biphosphonate % 2 1.Hoff AO, Ann NY Acad Sci 1218: 47-54; Guarneri V Breast Cancer Res Treat 122: ; McArthur HL, ASCO 2008; abstr 9588
Bevacizumab and osteonecrosis of the jaw
Meta-analyses evaluating the safety of bevacizumab EventIncidenceRR Hypertension grade %12 Left ventricular dysfunction/CHF grade %4.7 Hemorrhage grade %4.07 Arterial/venous embolism Grade %1.7 (ns) Cortes, Ann Oncol 2011; Ranpura JAMA 2011; Choueiri JCO 2011