CAELYX CLINICAL TRIALS Metastatic Breast Cancer (MBC)

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


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%


NR31% (A)/ 18% (B)11% (B)


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%


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


Baseline Patient Demographics


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


CAELYX(N=254)


(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


CAELYX(N=254)


(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


CAELYX(N=254)


(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


CAELYX(N=254)


(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*


CAELYX(N=209)


(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


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


CAELYX vs Doxorubicin- Cardiac Events -


CAELYX(N=254)


(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


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


HR = 3.16 (95% CI: 1.58-6.31); P < .001

CAELYX vs DoxorubicinLVEF vs Cumulative Dose

All < 300 ≥ 300 to < 450 ≥ 450

CAELYX


-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)


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


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)


(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*


% 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


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


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


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


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


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)


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.


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


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


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


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%


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%


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%


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%


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

Documents

CAELYX CLINICAL TRIALS Metastatic Breast Cancer (MBC)