Terapie antiangiogenetiche: revisione e gestione degli eventi avversi
description
Transcript of Terapie antiangiogenetiche: revisione e gestione degli eventi avversi
![Page 1: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/1.jpg)
Terapie antiangiogenetiche: revisione e gestione degli eventi avversi
Lucia Del MastroSS Sviluppo Terapie InnovativeModena- 18 Novembre 2011
IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro
![Page 2: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/2.jpg)
![Page 3: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/3.jpg)
• 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
![Page 4: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/4.jpg)
• 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
![Page 5: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/5.jpg)
Relationship between cause of death and study drugs changed in 65%of patients -> underestimation by local investigators of the relation between theadministration of study drugs and death
![Page 6: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/6.jpg)
![Page 7: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/7.jpg)
![Page 8: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/8.jpg)
![Page 9: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/9.jpg)
Beva vs contlAVF2119g: 0 eventsE2100: 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
![Page 10: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/10.jpg)
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
![Page 11: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/11.jpg)
Beva: 0.51%Cntl: 0.21%OR: 1.84P=0.327
Beva: 4.9%Cntl: 2.8%OR: 1.45 P=0.052
![Page 12: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/12.jpg)
Beva: 9.7%Cntl: 0.64%OR: 12.76 (2.93-55.53)P=0.001
OR: 27.68P<0.0001
![Page 13: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/13.jpg)
Beva: 1.31%Cntl: 0.28%OR: 4.07P=0.006
![Page 14: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/14.jpg)
Beva: 1.73%Cntl: 0.78%OR: 2.25 (1.16-4.37)P=0.017
![Page 15: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/15.jpg)
Beva: 1.6%Cntl: 0.4%RR 4.74 (1.66-11.18)P=0.001
![Page 16: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/16.jpg)
![Page 17: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/17.jpg)
![Page 18: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/18.jpg)
![Page 19: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/19.jpg)
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.
![Page 20: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/20.jpg)
![Page 21: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/21.jpg)
![Page 22: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/22.jpg)
![Page 23: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/23.jpg)
![Page 24: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/24.jpg)
Bevacizumab and osteonecrosis of the jaw
ONJ incidence
Biphosphonate alone 1-6%1
Bevacizumab alone 0.3-1% 2,3
Bevacizumab + biphosphonate 0.9-2.4% 2
1. Hoff AO, Ann NY Acad Sci 1218: 47-54; 20112. Guarneri V Breast Cancer Res Treat 122: 181-188; 20103. McArthur HL , ASCO 2008; abstr 9588
![Page 25: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/25.jpg)
Bevacizumab and osteonecrosis of the jaw
![Page 26: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/26.jpg)
![Page 27: Terapie antiangiogenetiche: revisione e gestione degli eventi avversi](https://reader036.fdocuments.net/reader036/viewer/2022062409/56814ea5550346895dbc50d9/html5/thumbnails/27.jpg)
Meta-analyses evaluating the safety of bevacizumab
Event Incidence RR
Hypertension grade 3-4 10-12% 12
Left ventricular dysfunction/CHF grade 3-4
1.6-1.8% 4.7
Hemorrhage grade 3-4 1.3% 4.07
Arterial/venous embolismGrade 3-4
4.2% 1.7 (ns)
Cortes, Ann Oncol 2011; Ranpura JAMA 2011; Choueiri JCO 2011