A	B	C	D
1	Main
2		Brand Name	Avastin
3		Generic Name	bevacizumab
4		Indication	1L mCRC, 2L mCRC, 1L mNSCLC, 1L mBC, 1L mRCC.
5			11/09: EMEA rejects for GBM.
6		Timeline	March 2007: Europe approval of Avastin in mBC.
7			February 2008: US approval of Avastin in mBC.
8		Economics	PDLI royalty.
9		Mechanism	VEGF recombinant humanized monoclonal antibody.
10		Competition	CT-322
11		Safety	High thromboembolism, GI tract perforation, neutropenia, pulmonary hemorrhage, hypertension and impairment of wound healing.
12		Papers	Risk of Venous Thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. Nalluri et al. JAMA 2008;300(19):2277-2285.
13			Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. Tol et al. NEJM 2009;360:563-72.
14			Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. Miller et al. NEJM 2007;357:2666-76.
15			Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomized, double-blind phase III trial. Escudier et al. Lancet 2007;370:2103-11.
16			Paclitaxel-Carboplatin alone or with bevacizumab for NSCLC. Sandler et al. NEJM 2006;355:2542-50.
17			Current perspective: bevacizumab in colorectal cancer - a time for reappraisal? Okines et al. Eu J of Cancer 45(2009);2452-2461.
18			Bevacizumab plus irinotecan, fluorouracil and leucovorin for metastatic colorectal cancer. Hurwitz et al. NEJM 2004;350:2335-42.
19		Clinical Trials
20			Phase III AVANT - adjuvant CRC n=3500 from 12/04-6/07. Data in 2010.
21			FOLFOX vs FOLFOX+Avastin with Avastin maintenance for 5.5m, Xelox+Avastin with Avastin maintenance for 5.5m.
22			DFS primary.
23
24			Phase III AVAGAST - 1L advanced gastric cancer - Data in 2010
25			Failed but showed trends
26
27			Phase III GOG-0218 - 1L mOC - Data in 2010
28			Avastin+Chemo+Maintenance Avastin had S.S. improvement in PFS vs chemo alone vs chemo+avastin.
29			14.1 months vs. 10.3, HR=0.72.
30
31
32			Phase III ICON-7 - 1L mOC - Data in 2010
33			Phase III CALGB-90401 - 1L mHRPC - Data in 2010. - Failed with worse mortality.
34
35			Phase III "C08" - adjuvant CRC - FAILED n=2710
36			1-year of beva treatment, 40% event reduction at one year. HR=0.6, p=0.0004.
37			77.4% alive at the end of 3 years versus 75.5% for chemo. HR=0.89, p=0.15.
38
39			Phase III 1L mBC "AVADO" - Taxotere +- Avastin - ASCO 2008
40			64% improvement in PFS (HR=0.61) in 15mg/kg.
41			45% improvement in PFS (HR=0.69) in 7.5mg/kg.
42			83%, 78% and 73% were alive in 15mg, 7.5mg and placebo.
43			Survival crossed.
44
45			Phase III 1L mBC "E2100" - Paclitaxel+-Avastin n=722 from 12/01 to 5/04. NEJM 2009, Miller et al.
46			11.8m PFS vs. 5.9m for chemo alone.
47			Failed to meet OS endpoint: 26.7m vs 25.2m.
48
49			Phase III mCRC "BEAT - Bevacizumab Expanded Access Trial" community-setting study n=2000
50			22.7m mOS.
51
52			Phase III mCRC "BRITE" community-setting study
53			23.5m mOS.
54
55			Phase III mNSCLC "SAIL" community-setting study
56			7.8m TTP, 14.6m OS.
57
58			Phase III mNSCLC "ARIES" community-setting study
59			Phase III mBC "ATHENA" community-setting study
60
61			Phase III "CAIRO2" CapeOxBeva+-Cetuximab n=755 1L mCRC. Tol et al NEJM 2009
62			10.7m mPFS for triplet vs 9.4-9.8m mPFS for quadruplet.
63			20.4m mOS for triplet vs 20.3m mOS for quadruplet.
64
65			Phase III 1L mNSCLC "AVAIL" Gem+Cis+Low-Dose Avastin vs High-Dose Avastin
66			PFS met primary endpoint while OS failed.
67
68			Phase III "ECOG 4599" n=878 1L mNSCLC Carbo+Tax+-Avastin Sandler et al NEJM 2006 (7/01-4/04)
69			12.3m mOS versus 10.3m mOS for chemotherapy alone.
70			6.2m mPFS versus 4.5m mPFS for chemotherapy alone.
71			4.4% significant bleeding versus 0.7%.
72
73			Phase III "E5103" n=3439/4950 enrollment halted due to CHF Avastin+Chemo in aBC
74			6 patients out of first 200 developed CHF.
75			Arm A: Doxorubicin+cyclophosphamide+placebo (4 cycles) followed by paclitaxel+placebo (4 cycles).
76			Arm B: Replace placebos with Avastin, Arm C: ArmB+ Avastin maintenance monotherapy for 10 cycles.
77
78			Phase II "BEAM" in stage IV metastatic melanoma n=214
79			Carbo+Tax+-Avastin. 5.6m PFS vs 4.2 for control. 12.3m OS vs 8.6m for control.
80
81			Phase II "BOXER" neoadjuvant mCRC
82			Avastin+Capecitabine+Oxaliplatin in mCRC confined to liver. ORR 80%.
83
84			Phase II "BRAIN"
85			Phase III "BEATRICE" triple-negative mBC
86
87			Phase III "RIBBON-1" mBC
88			HR=1.032 p=0.89 for OS
89
90			Phase III "AVOREN" n=649 mRCC Escudier et al. Lancet 2007
91			IFN+-Avastin mPFS 10.2m vs 5.4m for monotherapy. C25
92
93			Phase III "AVAPERL1"
94
95			Phase III "CAIRO3"
96
97			Phase III "ECOG 5202"
98
99			Phase III QUASAR2
100
101			Phase III "ECOG NSABP-ECOG E5204"
102
103			Phase III 1L mCRC n=813 Hurwitz et al NEJM 2004
104			20.3m mOS versus 15.6m for placebo.
105
106			Phase III adjuvant BC "B-46" n=3900 initiated May 2009, January 2022
107
108
109
110		IMS
111			11/1/2007	194
112			10/1/2007	196