CAELYXCAELYXCLINICAL TRIALSCLINICAL TRIALS
Metastatic Breast Cancer (MBC)Metastatic Breast Cancer (MBC)
Clinical Benefits of CAELYX in Breast Cancer
Anthracycline with cardiac sparing effect
– Significantly reduced risk of cardiotoxicity
– Preserves cardiac function for patients who can benefit from long-term anthracycline therapy
Comparable efficacy vs conventional doxorubicin Clinical evidence demonstrates improved safety profile:
Lower incidence: Higher incidence:– Nausea/vomiting – Hand-foot syndrome– Alopecia (HFS)– Myelosuppression – Stomatitis– Cardiotoxicity
CAELYX – Current Indications
Monotherapy for MBC in patients who are at increased cardiac risk
– Several studies demonstrating antitumor activity and acceptable tolerability in MBC and LABC
Advanced ovarian cancer in women who have failed a first-line platinum-based chemotherapy regimen
AIDS-related KS in patients with low CD4 counts (<200 CD4 lymphocytes/mm3) and extensive mucocutaneous or visceral disease
CAELYX in Breast Cancer: Target Populations
Rechallenge (eg, 1st-line treatment of MBC that responded to an anthracycline-containing regimen in adjuvant setting)
Combination therapy with trastuzumab
Patients with cardiovascular risk factors (eg, patients who present with hypertension, prior mediastinal irradiation, or a history of heart disease)
Elderly patients
Patients for whom the risk of specific toxicities are of significant concern (eg, alopecia, myelosuppression, N/V)
CAELYX Monotherapy
Sequential single-agent chemotherapy represents a reasonable option for patients with MBC
Monotherapy or sequential single-agent chemotherapy may be especially suitable for:
– Elderly or patients with poorer performance status
– Those unable to tolerate the toxicity ofcombination therapy
– Patients with slowly growing tumors
Single-Agent CAELYX for MBC: Phase II Studies
Ranson (JCO 1997)
Lyass (Cancer 2000)
No. of patients 71 45
Pt. population ~ 40% previously-treated
100% pretreated;69% ≥ 2 regimens; 71% previous anthracycline
CAEYLX regimen 45-50 mg/m2 q 3-4 wk x 6 cycles
35-70 mg/m2 q 3-6 wk
Efficacy – ORR 31% 33%
Safety Gr 3/4 neutropenia Gr 3/4 mucositis HFS
27%32%5% of cycles (45 mg/m2 Q 4 w)
Mild; dose-dependentDose-dependentSchedule-dependent
Single-Agent CAELYX for MBC: Phase II Studies
Coleman(Proc. SABCS 2002)
No. of pts (evaluable) 106
Pt. population Randomized; ≥ 65 yo or contraindication to standard anthra.; 33% pretreated
CAEYLX regimen (A) 60 mg/m2 q 6 wk -or- (B) 50 mg/m2 q 4 wk
Efficacy – ORR 20-23%
Safety Gr 3/4 neutropenia Gr 3/4 mucositis HFS
NR31% (A)/ 18% (B)11% (B)
Single-Agent CAELYX for MBC: Phase II Studies
Schmid(Proc. SABCS 2004)
Mlineritsch(Onkologie 2004)
No. of patients (evaluable) 24 (19) 30
Pt. population Heavily pretreated (med. prior regimens, 4); 88% prior anthra.; 83% prior taxane; cum. dox < 400 mg/m2 at entry
Failure of prior chemo for MBC (10% prior adjuvant anthra)
CAEYLX regimen 25 mg/m2 q 2 wk 45 mg/m2 q 4 wk
Efficacy – ORR 5% (CB* = 21%) 31%
Safety Gr 3/4 neutropenia Gr 3/4 mucositis HFS
0013% (no grade 4)
3% FN030% (all ≤ grade 2)
*Clinical Benefit =PR + SD > 6 mo.; 3 of 4 received prior anthra.
CAELYX 50 vs 40 mg/m2 in MBC: A Phase II Trial
Phase II
N = 53
Previously treated MBC
TREATMENT
CAELYX 40 mg/m2 q 4 wk
Al-Batran et al. Breast Cancer Res Treat. 2004; 88:S204. Abstract 5060. Updated based on poster.
Compared results to 50 mg/m2 trial of similar design
CAELYX 50 vs 40 mg/m2 in MBC: Outcomes
Al-Batran et al. Breast Cancer Res Treat. 2004; 88:S204. Abstract 5060. Updated based on poster.
50 mg/m2
(n=46)40 mg/m2
(n=45)
Efficacy ORR PFS, median OS, median
17%4.6 mo
13.8 mo
13%3.3 mo9.8 mo
Safety
Dose reduction, % pts
Median no. of cycles
Toxicity
Grade 3/4 HFS
Grade 3/4 Stomatitis
Grade 3/4 Neutropenia
28%
5
7%
17%
16%
7%
4
0%
2%
9%
CAELYX 40 mg/m2 q 4 wks*
Docetaxel 36 mg/m2 d 1, 8, 15 q 4 wks*
CAELYX vs Docetaxel in MBC: A Randomized Phase II Trial
Study Design• 1st-line MBC• Open-label,
crossover• Phase II
Eligibility• Prior adjuvant
anthracycline or taxane if ≥ 6 mo
• ≤ 300 mg/m2 of prior doxorubicin
• Normal LVEF
Yardley et al. Breast Cancer Res Treat. 2004;88:S203. Abstract 5057.
RANDOMIZATION
N = 73
*Max. 8 cycles prior to crossover†At time of progression
N = 36
N = 37
CROSSOVER†
CAELYX vs Docetaxel: Interim Results
CAELYX*
(n=36)
Docetaxel†
(n=37)
Median no. of cycles 2.5 4
Response rate (initial regimen) 17% 22%
Progression-free survival 6.9 mo 5.4 mo
Overall survival 15.8 mo 13.6 mo
Yardley et al. Breast Cancer Res Treat. 2004;88:S203. Abstract 5057. Updated based on poster.
*22 patients received drug on crossover; †18 patients received drug on crossover
CAELYX vs Docetaxel: Toxicity% of Pts
Grade 3 and 4 Toxicity CAELYX(n=36)
Docetaxel(n=37)
Neutropenia 14 14
Anemia 3 5
Transfusions 6 11
Fatigue 3 30
Arthralgia 3 11
Nausea 6 16
HFS 11 5
Stomatitis 14 5
Hospitalization 17 35
Yardley et al. Breast Cancer Res Treat. 2004;88:S203. Abstract 5057. Updated based on poster.
CAELYX 50 mg/m2 q 4 wks*
Conventional doxorubicin 60 mg/m2 q 3 wks†
*Until PD or unacceptable toxicity.
†Until PD or cumulative anthracycline dose of 550 mg/m2.
CAELYX vs Conventional Doxorubicin in First-line Treatment
of MBC: Phase III Trial
Study Design• 1st-line MBC
(Stages IIIB/IV)• Open-label,
multicenter
Stratification• Prior adjuvant
anthracycline• Cardiac risk factor• Bone only mets
O’Brien et al. Ann Oncol. 2004;15:440-449.
RANDOMIZATION
N = 509 68 international sites
CAELYX vs Doxorubicin Study Endpoints
Primary– Progression-free survival (non-inferiority)– Cardiotoxicity:
Cardiac event as defined by:• LVEF decrease of ≥ 20% from baseline if resting LVEF
remained in normal range
• LVEF decrease of ≥ 10% if resting LVEF became abnormal
Patients also assessed for clinical signs/symptoms of CHF
Secondary– Overall survival – Overall response rate– Tolerability
O’Brien et al. Ann Oncol. 2004;15:440-449.
Baseline Patient Demographics
O’Brien et al. Ann Oncol. 2004;15:440-449.
CAELYX(N=254)
Conventional Doxorubicin
(N=255)
Median age, years 59 58
Menopausal status, % Premenopausal Postmenopausal
3169
3562
Estrogen receptor status, % ER + ER -
3521
4023
WHO performance status, % 0 1 2
54379
494011
Baseline Disease Characteristics
O’Brien et al. Ann Oncol. 2004;15:440-449.
CAELYX(N=254)
Conventional Doxorubicin
(N=255)
No. of metastatic sites, %
1
2
≥ 3
37
33
30
41
31
28
Metastatic site classification, %
Visceral
Nonvisceral
Bone metastases only
59
32
9
56
34
10
Baseline DemographicsPrior Therapy
O’Brien et al. Ann Oncol. 2004;15:440-449.
CAELYX(N=254)
Conventional Doxorubicin
(N=255)
Prior therapy*, %
Adjuvant only Advanced disease only Adjuvant and advanced disease
65
5258
62
427
12
Prior conventional anthracycline, % 15 16
Baseline cum. anthracycline (mg/m2), % < 150 150-300 > 300
212< 1
2131
Previous radiation therapy, % 47 49*Chemotherapy or hormonal therapy.
Baseline Cardiac Risk Factors
O’Brien et al. Ann Oncol. 2004;15:440-449.
CAELYX(N=254)
Conventional Doxorubicin
(N=255)
No cardiac risk factors, % 52 53
Prior cardiac risk factors, %
Prior mediastinal irradiation
History of heart disease
History of hypertension
Age ≥ 65
≥ 2 risk factors
48
4
0.4
12
15
17
47
3
0.4
17
13
15
Results: Treatment Summary
O’Brien et al. Ann Oncol. 2004;15:440-449.
CAELYX(N=254)
Conventional Doxorubicin
(N=255)
Median duration of therapy, wks (cycles) 21 (5.3) 19 (6.3)
Mean dose per cycle, mg/m2 48 58
Mean cycle length, days 29.6 22.3
Median cum. anthracycline exposure*, mg/m2
293 361
Drug discontinuation, %
24 24
*Including prior anthracycline therapy
CAELYX vs Doxorubicin Response Rates*
O’Brien et al. Ann Oncol. 2004;15:440-449.
CAELYX(N=209)
Conventional Doxorubicin
(N=201)
Overall response rate (CR + PR) 33% 38%
Complete response (CR) 3% 4%
Partial response (PR) 29% 34%
Stable disease (SD) 25% 25%
Progressive disease (PD) 18% 11%
Median duration of response 7.3 mo 7.1 mo
*Measurable disease (n=410); 25% in each group had no radiographic assessment of response.
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 5 10 15 20 25 30 35
Months From Randomization
Pro
bab
ility
O’Brien et al. Ann Oncol. 2004;15:440-449.
CAELYX vs Doxorubicin Progression-Free Survival (PFS)
CAELYXConventional doxorubicin
Median PFS, mo. 6.9 7.8HR = 1.00 (95% CI: 0.82-1.22)
Intent-to-Treat Population
CAELYX vs DoxorubicinOverall Survival (OS)
Intent-to-Treat Population
HR = 0.94 (95% CI: 0.74-1.19); P = .59
CAELYXConventional doxorubicin
Median OS, mo. 21 22
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 5 10 15 20 25 30 35
Months From Randomization
Pro
bab
ility
O’Brien et al. Ann Oncol. 2004;15:440-449.
CAELYX vs Doxorubicin- Cardiac Events -
O’Brien et al. Ann Oncol. 2004;15:440-449.
CAELYX(N=254)
Conventional Doxorubicin
(N=255)
LVEF decrease
LVEF decrease + signs/symptoms of CHF
LVEF decrease alone
10
0
10
48
10
38
Signs and symptoms of CHF without LVEF decrease
2 2
Patients who stopped therapy due to cardiac event
6 36
CAELYX vs Doxorubicin Cardiac Events vs Cumulative Dose
O’Brien et al. Ann Oncol. 2004;15:440-449.
100
90
80
70
60
50
40
30
20
10
0
0 50 100 150 200 300250 400 450 500 550 600350Cumulative Anthracycline Dose
Kap
lan
-Mei
er E
stim
ates
of
Car
dia
c E
ven
ts
CAELYX
Conventional Doxorubicin
HR = 3.16 (95% CI: 1.58-6.31); P < .001
CAELYX vs DoxorubicinLVEF vs Cumulative Dose
All < 300 ≥ 300 to < 450 ≥ 450
CAELYX
Conventional Doxorubicin
-18
-16
-14
-12
-10
-8
-6
-4
-2
0
Med
ian
% C
han
ge
Fro
m B
asel
ine
Cumulative Anthracycline Dose (mg/m2)
O’Brien et al. Ann Oncol. 2004;15:440-449.
n=152
n=187
n=62
n=58
n=54
n=74
n=36
n=55
CAELYX vs Doxorubicin Cardiotoxicity in High-Risk Patients
NCardiotoxicity
EventsHR 95% CI
≥ 65 years of age
CAELYX
Doxorubicin
Prior adjuvant anthracycline
CAELYX
Doxorubicin
Cardiac Risk factor
CAELYX
Doxorubicin
78
66
38
40
122
121
0
9
1
11
5
21
N/A
7.27
2.7
N/A
0.93-56.80
1.01-7.18
O’Brien et al. Ann Oncol. 2004;15:440-449.
Treatment-Related Adverse EventsAll Grades
% P
ati
ents
12
20
37
19
4
23 22
2
16
66
53
31
1013 15
48
0
10
20
30
40
50
60
70
80
CAELYX ConventionalDoxorubicin
*
*Grade 2 alopecia = complete hair loss; grade 3-4 NA. O’Brien et al. Ann Oncol. 2004;15:440-449.
Treatment-Related Adverse Events: Alopecia
CAELYX(N=254)
Conventional Doxorubicin
(N=255)
Overall incidence 20% 66%
Pronounced or total hair loss 7% 54%
13
1 24 5
02
5 48
2 2
17
0
5
10
15
20
25
30
35
40
45
50
CAELYX ConventionalDoxorubicin
Treatment-Related Adverse EventsGrades 3/4*
O’Brien et al. Ann Oncol. 2004;15:440-449.
% P
ati
ents
*Grade 3-4 alopecia NA ; grade 2 alopecia = complete hair loss; cardiotoxicity not included.
Study Conclusions
CAELYX provides comparable efficacy to conventional doxorubicin
CAELYX has significantly less cardiotoxicity than conventional doxorubicin
– 7-fold reduction in risk of cardiotoxicity with CAELYX in pts previously treated with anthracyclines
CAELYX has a distinct side effect profile
– Significantly less alopecia, N/V, myelosuppression– Manageable HFS
CAELYX has an improved risk-benefit profile
O’Brien et al. Ann Oncol. 2004;15:440-449.
CAELYX 50 mg/m2 q 4 weeks
Study Design• MBC after taxane
failure (Stage IIIB/IV)• Open-label, multicenter• Phase III
Stratification• Number of prior
regimens (1 or 2)• Presence of bone
metastases only (yes/no)
CAELYX in MBC After Taxane Failure
Vinorelbine 30 mg/m2 weekly- OR -
Mitomycin C 10 mg/m2 d 1, 28Vinblastine 5 mg/m2 d 1, 14, 28, 42*
301 Patients 52 International sites
*Days 1-56 for 2 cycles; subsequent cycles: Mitomycin C on d 1 and vinblastine D1, 21; Mitomycin C dosed every 6 to 8 wks.Keller et al. J Clin Oncol. 2004;22:3893-3901.
RANDOMIZATION
N = 150
N = 129
N = 22
CAELYX in MBC After Taxane Failure Study Endpoints
Primary– Progression-free survival
Secondary– Overall survival– Overall response rate– Response duration– Event-free survival– Tolerability– QOL
Keller et al. J Clin Oncol. 2004;22:3893-3901.
Baseline CharacteristicsCAELYX(N=150)
Comparator(N=151)
Age, years 56 56
Postmenopausal, % 54 56
Estrogen Receptor Status, % Positive Negative
4733
4832
Sites of Metastasis, % Visceral Bone only
6310
6610
Previous Chemotherapy Regimens, n 1 2 1 only bone mets 2 only bone mets
222323
222323
Keller et al. J Clin Oncol. 2004;22:3893-3901.
Prior Therapy
CAELYX(N=150)
Comparator(N=151)
Adjuvant therapy, % 78 73
Hormonal therapy, % 65 59
Chemotherapy, % Adjuvant only Advanced disease only Adjuvant plus advanced disease
42274
42769
Keller et al. J Clin Oncol. 2004;22:3893-3901.
Prior Therapy (cont.)
CAELYX(N=150)
Comparator(N=151)
Regimens for advanced dz, % 1 2
5635
5236
Anthracycline exposure, % 83 84
Cumulative prior anthracycline dose (mg/m2), % 0-300 >300-450 >450
61175
52263
Primary anthracycline resistance, % 39 35
Radiation therapy, % 77 71
Keller et al. J Clin Oncol. 2004;22:3893-3901.
CAELYX in MBC After Taxane Failure Response Rates
CAELYX(N=115)
Comparator(N=117)
Overall Response (CR + PR)
Complete Response (CR)
Partial Response (PR)
Stable Disease (SD)
Progressive Disease (PD)
10%
2%
8%
28%
32%
12%
2%
10%
28%
32%
Median Duration of Response 5.7 months 6.0 months
Keller et al. J Clin Oncol. 2004;22:3893-3901.
CAELYX in MBC After Taxane Failure Progression-Free Survival (PFS)
Months
Pro
gre
ssio
n-F
ree
Su
rviv
al
CAELYX Comparator
Median PFS, mo. 2.9 2.5
HR = 1.26 (95% CI: 0.98-1.62)
Keller et al. J Clin Oncol. 2004;22:3893-3901.
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 3 6 9 12
CAELYX in MBC After Taxane Failure Overall Survival (OS)
Ov
era
ll S
urv
iva
l
0.0
0.2
0.4
0.6
0.8
1.0
0 3 6 9 12 15 18Months
CAELYX Comparator
Median OS*, mo. 11 9
HR = 1.05 (95% CI: 0.82-1.33)
*Data updated in Keller et al. J Clin Oncol. 2004;22:3893-3901.
Data on file Schering-Plough.
Progression-Free Survival by Subgroup
Subgroups analyzed retrospectively based on protocol-eligible patients.
Keller et al. J Clin Oncol. 2004;22:3893-3901.
CAELYX is effective independent of patient subsets
Patient Population/Subgroups
Protocol Evaluable (115/117)
Age < 55 (49/55)
Age ≥ 55 (66/62)
Performance ≥ 80% (93/99)
Performance < 70% (22/18)
Bone Only (11/11)
Not Bone Only (104/106)
With Any Anthracycline Exposure (92/96)
With No Anthracycline Exposure (23/21)
With Anthracycline Resistance (46/34)
With No Anthracycline Resistance (69/80)
Estrogen Recept: Negative (41/40)
Estrogen Recept: Positive (54/56)
Number of Chemo Regimens < 2 (72/72)
Number of Chemo Regimens ≥ 2 (43/45)
Disease-Free Interval ≤ 24 (52/65)
Disease-Free Interval > 24 (63/52)
Hazard Ratio with a 95% C.I.0 0.8 1 2 3
Treatment-Related Adverse EventsAll Grades
37
20
3
31
20
3
14
22
1
5
9
0.8
21
5
27
1714
0.8
4
11
16 15
0
9
0
23
18
5 5
0
5 5
32
0
5
10
15
20
25
30
35
40
45
50
HFS
Fatig
ue
Alope
cia
Nause
a
Vomiti
ng
Neutro
penia
Muc
ositis
Stom
atiti
s
Neuro
pathy
Const
ipat
ion
Asthe
nia
CAELYX (n=150) Vinorelbine (n=129) Mitomycin C + Vinblastine (n=22)
Per
cen
t o
f P
atie
nts
Keller et al. J Clin Oncol. 2004;22:3893-3901.
Treatment-Related Adverse EventsGrades 3/4
19
43
42
35
0 01
02
7
3
8
0 0 0.82
4
0
5 5
0 0 0 0 0 0 00
5
10
15
20
25
30
HFS
Fatig
ue
Nause
a
Vomiti
ng
Neutro
penia
Muc
ositis
Stom
atiti
s
Neuro
pathy
Const
ipat
ion
Asthe
nia
CAELYX (n=150) Vinorelbine (n=129) Mitomycin C + Vinblastine (n=22)
Per
cen
t o
f P
atie
nts
Keller et al. J Clin Oncol. 2004;22:3893-3901.
Cardiac Toxicity
Defined per protocol as a decrease in LVEF of ≥ 15 points from baseline or a ≥ 5-point decrease from baseline if level is below LLN for the institution
LVEF changes assessed only in patients receiving CAELYX– 22 patients had LVEF changes consistent with protocol-
defined cardiac toxicity
– No correlation with cumulative anthracycline dose
– 4 patients dc’d drug due to LVEF decrease
No patient developed clinical CHF
Study Conclusions
CAELYX demonstrates activity in MBC after taxane failure:
– PFS: 2.9 months (vs 2.5 months comparator)– OS: 11.0 months (vs 9.0 months comparator)
CAELYX has comparable efficacy to vinorelbine/mitomycin for MBC refractory to taxane-based therapies
– q 4 wk CAELYX = q wk vinorelbine administration
CAELYX represents a therapeutic option for pts with heavily pretreated, taxane-refractory MBC
Keller et al. J Clin Oncol. 2004;22:3893-3901.
CAELYX Combination CAELYX Combination Therapy for MBCTherapy for MBC
Rationale for CAELYX Combinations
Preclinical synergy
Non-overlapping mechanisms/toxicities
Polychemotherapy, in particular with taxane-anthracycline-based regimens, is especially suitable for patients with:
– Life-threatening disease– Symptomatic visceral metastatic disease– Quickly growing tumors– Ability to tolerate the toxicity of combination therapy
CAELYX CombinationsBreast Cancer
Investigators Combination Response
Overmoyer 1998; Silverman 1999; Srimuninnimit 2002
PLD + cyclophosphamide 41%-68%
Jones 2000; Gogas 2002; Rigatos 2003; Vorobiof 2004; Fulfaro 2004
PLD + paclitaxel 56%-75%
Sparano 2001; Holmes 2003; Alexopoulos 2004; Morabito 2004
PLD + docetaxel 32%-64%
Martin 2002; Gebbia 2002; Ardavanis 2003
PLD + vinorelbine 36%-68%
Rivera 2003; Fabi 2004 PLD + gemcitabine 48%-52%
Guastalla 2003 PLD + cyclophosphamide + 5-fluorouracil
CAELYX + Cyclophosphamide in BC
Silverman (Proc. ASCO 1999)
Srimuninnimit(Proc. ASCO 2002)
No. of patients / med. cycles 20 / NR 30 / NR
Pt. population Untreated (n=6) or previously treated MBC; prior adjuvant anthra. (n=3)
LABC: T3 (n=7); T4 (n=23)
Regimen CAELYX Cyclophosphamide
Q 3 wk30 mg/m2 d 1600 mg/m2 d 1
Q 3 wk x 335 mg/m2 d 1600 mg/m2 d 1
Efficacy – ORR* 60% 73%
Safety G 3/4 neutropenia FN G 3/4 HFS Cardiac
Moderate 25%NRMild 15%NR
37%NR3%NR
CAELYX + Paclitaxel in MBCVorobiof (Breast 2004)
Rigatos (Oncol Rep 2003)
No. of patients
No. of cycles, median
34
6
24
Not reported
Pt. population 1st line for MBC; 41% received adjuvant chemo- or chemoendocrine therapy (anthra.: 2 pts)
1st line for MBC; all evaluable pts received prior adjuvant chemotherapy
Regimen CAELYX Paclitaxel
Q 3 wk30 mg/m2
175 mg/m2
Q 3 wk30 mg/m2
175 mg/m2
Efficacy – ORR 73% 70% (23 evaluable)
Safety per patient G 3/4 neutropenia FN G 3/4 HFS Cardiac
2 toxic deaths21%6%29%1 pt LVEF ↓ > 20%
22%Not reported48%1-arrhythmia1-LVEF ↓ (not defined)
Neoadjuvant CAELYX + Paclitaxel in LABC
Phase II
N = 35
Newly diagnosed LABC
TREATMENT
CAELYX 35 mg/m2 d 1
+
Paclitaxel 175 mg/m2 d 1
q 3 wk
RESULTSORR 71% (CR 17%, PR
54%)
pCR after 4-6 cycles 3 pts
Grade 3 HFS 9%
Grade 3/4 neutropenia 15%
Alopecia 83% Gogas et al. Ann Oncol. 2002;13:1737-1742.
CAELYX + Docetaxel in MBC
Alexopoulos(Ann Oncol 2004)
Holmes(Proc. SABCS 2003)
No. of patients / med. cycles 44 / 6 48 / 4
Pt. population 1st line for MBC; 46% received prior adjuvant chemotherapy; 23% anthra.-based
1st line for MBC; 48% received prior adjuvant chemotherapy
Regimen CAELYX Docetaxel
Q 3 wk30 mg/m2
75 mg/m2
Q wk x 3; Q 28 d10 mg/m2
25 mg/m2
Efficacy – ORR* 64% 32%
Safety G 3/4 neutropenia FN G 3/4 HFS Cardiac
18%9%2%Anthra-pretx: mean Δ in LVEF of 4%
2%4%6%NR
*Assessable pts
CAELYX + Docetaxel in MBC
Morabito(Breast Caner Res Treat 2004)
No. of patients / med. cycles 33/4
Pt. population 1st line for MBC; LABC pts included and evaluated separately
Regimen CAELYX Docetaxel
Q 3 wk35 mg/m2
35 mg/m2 d 2, 9
Efficacy – ORR* 64%
Safety G 3/4 neutropenia FN G 3/4 HFS Cardiac
9%0%14%NR
*Assessable pts
CAELYX + Vinorelbine in MBCMartin(Clin Breast Ca 2004)
Gebbia (Oncology 2002)
Ardavanis(ASCO 2003)
No. of patients / med. cycles
35 / 6 30 (18 / 6†) 32 / 3
Pt. population Prior anthra. therapy in adjuvant or metastatic setting
100% received prior adjuvant chemotherapy; no pt had prior chemo for MBC
Taxane- or anthra.-pretx’d
Regimen CAELYX Vinorelbine
Q 4 wk35 mg/m2 d 130 mg/m2 d 1
Q 15 d20 mg/m2
30 mg/m2
Q 4 wk40 mg/m2 d 125 mg/m2 d 1, 15
Efficacy – ORR* 35% 68% (63%†) 41%
Safety G 3/4 neutropenia FN G 3/4 HFS Cardiac
44% (G 4)9%6%3 pt had LVEF ↓ (not defined)
39%†
--†
01 pt had 15% ↓ in LVEF†
53%--NRNR
*Assessable pts†Phase II portion
CAELYX + Gemcitabine in MBCRivera(JCO 2003)
Fabi (ASCO 2004)
No. of patients / med. cycles 49 / 6 28 / 5
Pt. Population Previously untreated; 57% received prior adjuvant chemo; 39% prior adjuvant anthra.
Untreated (n=15) or previously treated MBC (1 or 2 prior regimen); 39% received prior anthra.
Regimen CAELYX Gemcitabine
Q 3 wk24 mg/m2 d 1800 mg/m2 d 1, 8
Q 3 wk25 mg/m2 d 1800 mg/m2 d 1, 8
Efficacy – ORR* ORR anthra. pretx’d
52%58%
48%36%
Safety G 3/4 neutropenia FN G 3/4 HFS Cardiac
74%2%6%1 pt LVEF ↓ of 21% (had prior med. XRT)
39%3.5%----
*Assessable pts
CAELYX Combinations Conclusions
Phase II studies of CAELYX combinations demonstrate considerable activity in the treatment of MBC
Most combinations utilize a CAELYX dosage of 25-35 mg/m2 on a Q 3 wk schedule
Regimens have been generally well tolerated
CAELYX is a rational substitute for conventional anthracyclines in combination therapy for MBC
CAELYX in Breast Cancer: Conclusions
CAELYX is a novel anthracycline with established efficacy in MBC
CAELYX is associated with a distinct safety profile– Reduced rates of alopecia, nausea/vomiting, and
myelosuppression; manageable hand-foot syndrome; and, preservation of cardiac function
CAELYX offers a convenient regimen for various subgroups of MBC patients, including in the setting of anthracycline rechallenge
Phase II studies of CAELYX combinations demonstrate considerable activity and tolerability
CAELYX is a rational substitute for conventional doxorubicin in combination therapy for MBC
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