Terapie antiangiogenetiche: revisione e gestione degli eventi avversi Lucia Del Mastro SS Sviluppo Terapie Innovative Modena- 18 Novembre 2011 IRCCS Azienda.

Presentazione sul tema: "Terapie antiangiogenetiche: revisione e gestione degli eventi avversi Lucia Del Mastro SS Sviluppo Terapie Innovative Modena- 18 Novembre 2011 IRCCS Azienda."— Transcript della presentazione:

1 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

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3 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

4 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

5 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

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9 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: 0.642 (95% CI 0.334-1.232; p=0.183

10 ATEs: Beva: 0.93% Cntl: 0.56 OR: 1.49 (0.69-3.19) P=0.3 VTEs: Beva: 2.6% Cntl: 2.6% OR: 1.06 (0.70-1.61) P=0.78

11 Beva: 0.51% Cntl: 0.21% OR: 1.84 P=0.327 Beva: 4.9% Cntl: 2.8% OR: 1.45 P=0.052

12 Beva: 9.7% Cntl: 0.64% OR: 12.76 (2.93-55.53) P=0.001 OR: 27.68 P<0.0001

13 Beva: 1.31% Cntl: 0.28% OR: 4.07 P=0.006

14 Beva: 1.73% Cntl: 0.78% OR: 2.25 (1.16-4.37) P=0.017

15 Beva: 1.6% Cntl: 0.4% RR 4.74 (1.66-11.18) P=0.001

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19 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.

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24 Bevacizumab and osteonecrosis of the jaw ONJ incidence Biphosphonate alone1-6% 1 Bevacizumab alone0.3-1% 2,3 Bevacizumab + biphosphonate0.9-2.4% 2 1.Hoff AO, Ann NY Acad Sci 1218: 47-54; 2011 2.Guarneri V Breast Cancer Res Treat 122: 181-188; 2010 3.McArthur HL, ASCO 2008; abstr 9588

25 Bevacizumab and osteonecrosis of the jaw

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27 Meta-analyses evaluating the safety of bevacizumab EventIncidenceRR Hypertension grade 3-410-12%12 Left ventricular dysfunction/CHF grade 3-4 1.6-1.8%4.7 Hemorrhage grade 3-41.3%4.07 Arterial/venous embolism Grade 3-4 4.2%1.7 (ns) Cortes, Ann Oncol 2011; Ranpura JAMA 2011; Choueiri JCO 2011