18 November 2005 ODAC: DOXIL®, AIDS-related KS
Studies of DOXIL for AIDS-related KS(Pre-HAART)
Study No. Design
No. of pts. Objective Response Rate/Results
30-10 Phase 3 comparison to ABV
258 DOXIL (46.2%) vs. ABV (25.6%)
30-11 Phase 3 comparison to BV 241 DOXIL (58.7%) vs. BV (23.3%)
30-12 Open-label, non-comparative extension
871 DOXIL (65.9%) (n = 41 patients w/prior therapy)
30-14 Randomized, crossover, PK and tumor localization
43 DOXIL selectively accumulates into KS lesions
No significant differences in PK parameters b/w doses
30-21 Phase 1/2, cardiac biopsy data; comparison to cardiac damage
10 Less myocardial damage observed in patients treated with DOXIL compared to their matched doxorubicin controls
Note: A total of 10 DOXIL studies of varying design were completed for AIDS related KS
28 November 2005 ODAC: DOXIL®, AIDS-related KS
Publications of DOXIL for AIDS-related KS(HAART Era)
Study No. DesignDOXIL Treatment
(mg/m2)No. of pts. Results
Nunez Prospective, non-comparative, multicenter
DOXIL + HAART 79 79% response rate
Median time to response ~ 42 days
Martin-Carbonero
Randomized, open-label, multicenter
DOXIL 20mg/m2 every 3-weeks
28 20% HAART (N = 15)
76% HAART + DOXIL (N = 13)
Lichterfeld Uncontrolled, multicenter, observational study with matched controls
DOXIL + HAART 108 81.5% response rate
Recovery of CD4 counts not impaired by combination therapy
Hernandez Prospective, single arm, open-label, single center
DOXIL 20 mg/m2 every 3-weeks for 6 cycles
15 100% - GI response rate
53% Cutaneous response rate
38 November 2005 ODAC: DOXIL®, AIDS-related KS
Results of Randomized Studies of Liposomal Anthracyclines
NOTE: # = number; eval. = evaluable; A = Adriamycin (doxorubicin); B = bleomycin; V = vincristine; NS = not significant; NR = not reported. * includes complete and partial responses † this study reported mean survival times of 239 days for DOXIL, versus 160 days for bleomycin and vincristine.
Reference Treatment# entered
(# eval)Objective Response
Rate (%)*Time-to-treatment
failure (days)
Gill et al, 1996
DaunoXome 117 (116) 25%p=NS
115p=0.13
ABV 115 (111) 28% 99
Northfelt et al, 1998
DOXIL (2 Weeks) 133 (133) 46%
p<0.001124
p=0.26ABV 125 (125) 25% 128
Stewart, et al, 1998 †
DOXIL (3 Weeks) 121 (116) 59% p<0.001 160
p=NRBV 120 (102) 23% 157
48 November 2005 ODAC: DOXIL®, AIDS-related KS
Documentation for ACTG Criteria Biopsy Cutaneous lesions
– Number– Character (flat or raised)
Tumor-associated edema 3-5 marker lesions
– Bi-dimensional measurement Visceral lesions
– Radiographic evaluation – Bronchoscopy and endoscopy
58 November 2005 ODAC: DOXIL®, AIDS-related KS
Clinical Presentation of Patients Treated with DOXIL
Advanced KS with:– No prior HAART– HAART intolerant or failure– Virologic and immunologic response to HAART
Rapid KS progression on starting HAART (IRIS)
68 November 2005 ODAC: DOXIL®, AIDS-related KS
Response of Kaposi’s Sarcoma to DOXIL
78 November 2005 ODAC: DOXIL®, AIDS-related KS
Response of Kaposi’s Sarcoma to DOXIL
88 November 2005 ODAC: DOXIL®, AIDS-related KS
Response of Kaposi’s Sarcoma to DOXIL
98 November 2005 ODAC: DOXIL®, AIDS-related KS
Kaposi Sarcoma Incidence
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
5.5
1975
1976
1977
1978
1979
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
Year of diagnosis
Rat
e pe
r 100
,000 Study 30-38
Source: SEER Cancer Statistics Review, 1975-2002
AIDS-related KS approval