Abraxane Core SPRK Slide Set

ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound)
Abraxis Oncology and AstraZeneca

Clinical Forum
ABRAXANE® for Injectable
Suspension
(paclitaxel protein-bound particles for injectable
suspension) (albumin-bound)
Treatment in Metastatic Breast

Cancer
Indication
• ABRAXANE for Injectable Suspension (paclitaxel
protein-bound particles for injectable suspension)
(albumin-bound) is indicated for the treatment of breast
cancer after
– Failure of combination chemotherapy for metastatic
disease OR
– Relapse within 6 months of adjuvant chemotherapy
• Prior therapy should have included an anthracycline
unless clinically contraindicated
ABRAXANE [prescribing information]. Los Angeles, Calif: Abraxis Oncology, a Division of Abraxis BioScience,
Inc; May 2007.
Boxed Warning
• ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles
for injectable suspension) should be administered under the supervision
of a physician experienced in the use of cancer chemotherapeutic
agents. Appropriate management of complications is possible only when
adequate diagnostic and treatment facilities are readily available.
• ABRAXANE therapy should not be administered to patients with
metastatic breast cancer who have baseline neutrophil counts of less
than 1,500 cells/mm3. In order to monitor the occurrence of bone marrow
suppression, primarily neutropenia, which may be severe and result in
infection, it is recommended that frequent peripheral blood cell counts be
performed on all patients receiving ABRAXANE.
• Note: An albumin form of paclitaxel may substantially affect a drug’s
functional properties relative to those of drug in solution.
• DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL
FORMULATIONS.
Inc; May 2007.
ABRAXANE Presentation Overview

• Limitations of solvent-based paclitaxel
• Clinical pharmacology
• Pivotal phase III trial
– Efficacy
– Safety and tolerability
• Warnings and precautions, and contraindications
• Dosing and administration
Limitations of Solvent-based Paclitaxel

• Paclitaxel is a hydrophobic chemotherapeutic agent
• Conventional, solvent-based paclitaxel requires a

polyoxyethylated castor oil derivative, Cremophor® EL (CrEL) as a
formulation vehicle for parenteral administration
• CrEL has been implicated in adverse reactions seen with

solvent-based paclitaxel
– Hypersensitivity reactions
– Sensory neuropathy
• CrEL may alter the pharmacokinetics of paclitaxel

ten Tije et al. Clin Pharmacokinet. 2003;42:665-685.
Gelderblom et al. Eur J Cancer. 2001;37:1590-1598.
van Zuylen et al. Invest New Drugs. 2001;19:125-141.
Impact of Cremophor® EL on Paclitaxel

Therapy
Impact on Therapy
Premedication with steroids

Hypersensitivity reactions
and antihistamines
Cumulative peripheral sensory

Sensory nerve damage
neuropathy
Nonlinear pharmacokinetics
Entrapment of paclitaxel in
CrEL micelles Reduced systemic clearance
Reduced distribution to tissues
ten Tije et al. Clin Pharmacokinet. 2003;42:665-685.

Gelderblom et al. Eur J Cancer. 2001;37:1590-1598.
van Zuylen et al. Invest New Drugs. 2001;19:125-141.
ABRAXANE Product Description

ABRAXANE is free of Cremophor® EL, consisting of only
paclitaxel and albumin
• ABRAXANE is an albumin-bound form of paclitaxel
with a mean particle size of approximately 130
nanometers
• Albumin is a human protein and carrier of hydrophobic
nutrients, vitamins, steroids, and other compounds
• ABRAXANE takes advantage of the biological
properties of albumin to make water-insoluble
paclitaxel available to tissues
Inc; May 2007.
ABRAXANE has Linear Pharmacokinetics

Over Clinically Relevant Dose Range
• Linear PK over relevant dose range (solvent-based paclitaxel has nonlinear PK)1
• 43% faster clearance versus solvent-based paclitaxel1
• 53% larger volume of distribution versus solvent-based paclitaxel1
Mean AUC vs ABRAXANE Doses Studied (infused over 30 minutes)2,3

20000
Mean AUC (ng*hr/mL)
15000
10000
5000
-5000
75 100 125 150 175 200 225 250 275 300
n= 3 6 5 1 3 3 2/3 5
ABRAXANE Dose (mg/m2)

1
ABRAXANE [prescribing information]. Los Angeles, Calif: Abraxis Oncology, a Division of Abraxis BioScience, Inc; May
2007.
2
Nyman et al. J Clin Oncol. 2005;23:7785-7793.
3
Ibrahim et al. Clin Cancer Res. 2002;8:1038-1044.
ABRAXANE Clinical Experience
Efficacy in Metastatic
Breast Cancer
Nov 2005
Phase III Trial Design
ABRAXANE 260 mg/m2

IV over 30 min q 3 weeks
No Standard Premedication Required
Randomization (1:1)
n=460
Solvent-based Paclitaxel 175 mg/m2

IV over 3 hrs q 3 weeks
Standard Premedication with
Dexamethasone and Anti-histamines
Required
Gradishar et al. J Clin Oncol. 2005;23:7794-7803.

Inclusion Criteria
• Females at least 18 years of age
• Measurable metastatic breast cancer
• ECOG performance status 0 to 2
• No prior taxane therapy for metastatic disease

Study Population
• 460 patients randomized1
– Efficacy analyses based on randomized population1
• ABRAXANE 233 patients
• Solvent-based paclitaxel 227 patients
– Patients stratified for prior anthracycline exposure2
• 454 patients received at least one dose of drug1

– Toxicity analyses based on treated population1
• ABRAXANE 229 patients
• Solvent-based paclitaxel 225 patients
1
Inc; May 2007.
2
Primary Site of Metastatic Disease

ABRAXANE Solvent-based
n=229 paclitaxel
n=225
Mean Age 53 years 53 years
Liver 40% 43%
Lung 32% 35%
Only lymph nodes, soft tissue, and/or 16% 13%
breast
Bone 6% 6%
Abdominal 4% 3%
Unknown 1% 0%

Prior Chemotherapy
n=229 paclitaxel n=225
Anthracycline: adjuvant and/or metastatic 77% 78%

Anthracycline for metastatic disease 50% 58%
Prior chemotherapy for metastatic disease
None 42% 40%
1 prior regimen 41% 43%
2 prior regimens 10% 16%
≥ 3 prior regimens 7% 2%

Dose Delivered
n=229 paclitaxel n=225
Median cycles/patient 6 5
Mean cycles/patient 5.6 5.2
Mean dose/m2/cycle 255 mg 171 mg
Mean percentage of protocol dose 98% 98%
Mean total paclitaxel/patient/m2 1459 mg 909 mg
Median total paclitaxel/patient/m2 1560 mg 875 mg
O’Shaughnessy et al. Presented at: San Antonio Breast Cancer Symposium; December 3-6, 2003; San Antonio, TX.
Data on file. DA-ABR-01, Abraxis BioScience, Inc.
Concomitant Medications: Percent of Cycles

1293 cycles paclitaxel 1174
cycles
Non-5-HT3 antiemetics 2% 2%
5-HT3 antagonists 16% 14%
Any steroid medication 8% 98%
Steroids for HSR prophylaxis* 2% 95%
Colony-stimulating factors <1% 3%
HSR-Hypersensitivity reactions
*Any steroid started day before or day of study drug dosing
Reconciled Target Lesion Response Rate

• Reconciliation of response rates (FDA requirement)
– Reconciled target lesion response rate
• Primary endpoint and basis for FDA approval
– Independent Radiologic Laboratory
• Blinded to treatment
• Radiologic data during the first 6 cycles only
• Response rates typically lower than investigator reported
responses
– Investigator’s assessment
• Assessed both target and nontarget lesions throughout the
entire study duration
– Reconciliation algorithm
• Prospectively defined
Inc; May 2007.
Nearly Doubled Response Rate

Reconciled Target Lesion Response Rates
(Package Insert)
30 ABRAXANE
Solvent-based
25 p=0.003* paclitaxel
21.5%
p=NS
20
15.5%
15
11.1%
10 8.4%
5
st nei t a pf o e gat necr e P
0
n=233 n=227 n=129 n=143
All randomized patients Patients who had failed combination

chemotherapy or relapsed within 6 months of
adjuvant chemotherapy
* From Cochran-Mantel-Haenszel test stratified by 1st line vs >1st line therapy.
ABRAXANE [prescribing information]. Los Angeles, Calif: Abraxis Oncology, a Division of Abraxis BioScience, Inc; May 2007.
ABRAXANE Phase III Trial
Safety and Tolerability

Hematologic Toxicities
ABRAXANE Solvent-based paclitaxel
n=225
n=229
p-Value*
Grade 3 Grade 4 Grade 3 Grade 4
Neutropenia 25% 9% 31% 22% <0.001
Thrombocytopenia <1% 0% <1% 0% 0.387
Anemia <1% <1% 0% 0% 0.192
Febrile neutropenia <1% <1% <1% 0% 0.491
Septic deaths 0 0 --
*Cochran-Mantel-Haenszel test based upon all grades.
Neutropenia
• Significantly lower incidence of grade 4 neutropenia
– 9% (20/226) of patients treated with ABRAXANE
compared to 22% (48/222) of patients treated with
solvent-based paclitaxel (p<0.001)1, 2
• Overall incidence of neutropenia (<2.0 x 109/L)
– 80% of ABRAXANE-treated patients vs 82% of
patients treated with solvent-based paclitaxel2
1
2
Inc; May 2007.
Non-Hematologic Toxicities
Adverse Event ABRAXANE Solvent-based
n=229 paclitaxel
n=225
Grade Grade
2 3 4 2 3 4 p-Value*
Hypersensitivity <1% 0% 0% 0% 1% 0% 0.150
Flushing <1% 0% 0% 5% 0% 0% <0.001
Sensory neuropathy 20% 10% 0% 10% 2% 0% <0.001
Fatigue 13% 8% <1% 16% 3% <1% 0.062
Myalgias 12% 7% 0% 15% 2% 0% 0.567
Vomiting 4% 3% <1% 4% 1% 0% 0.022
Edema 2% 0% 0% <1% <1% 0% 0.851
*Cochran-Mantel-Haenszel test based upon all grades.
Hypersensitivity Reactions
• No severe hypersensitivity reactions (HSRs) were
observed with ABRAXANE in the randomized trial*
– 2% incidence of severe HSRs in solvent-based
paclitaxel arm
• 4% of patients in the ABRAXANE arm experienced
HSRs of any grade compared to 12% in the
solvent-based paclitaxel arm
* During postmarketing surveillance, rare occurrences of severe hypersensitivity reactions

have been reported with ABRAXANE
Inc; May 2007.
Neuropathy
• In the randomized trial, 10% (24/229) of patients in the ABRAXANE arm
developed grade 3 sensory neuropathy vs 2% of patients in the solvent-
based paclitaxel arm (p<0.001)1,2
– 14 out of 24 (58%) ABRAXANE-treated patients with grade 3 sensory
neuropathy had improvement to grade 2 or less within a median of 22
days1
• 10/14 patients who had improvement resumed treatment at a
reduced dose of ABRAXANE1
• No patients developed grade 4 sensory neuropathy in the ABRAXANE or
solvent-based paclitaxel arms1
• 3% (7/229) of patients discontinued ABRAXANE due to sensory neuropathy
of any grade vs <1% in the solvent-based paclitaxel arm3
• No severe motor neuropathy observed1
1
2
3
Time to Improvement of Grade 3 Neuropathy

1.00 *
* ABRAXANE (n=24)
0.75
Proportion not resolved
*
0.50
ABRAXANE Median Time to Improvement: 22

0.25 days
(95% CI: 17-22 days)
0.00
0 10 20 30 40 50 60 70 80 90 100 110 120 130

Days from grade 3 to lower grade
*Censored

Other Toxicity Results

• No patients had severe edema
• Nail changes were uncommon
• Ocular toxicity/visual disturbances occurred in 13% of
patients from the Phase III and single arm studies
– 1% were severe (keratitis and blurred vision)
• Severe cases were reported in patients who
received higher than recommended doses of
ABRAXANE (300 mg/m2 or 375 mg/m2) in a single
arm trial
– These effects were generally reversible
Inc; May 2007.
Toxicity Results: Geriatric Use

• 11% of patients in the randomized study who received
ABRAXANE were at least 65 years of age
• No toxicities occurred notably more frequently among the

elderly patients who received ABRAXANE
Inc; May 2007.
Warnings
• The use of ABRAXANE has not been studied in patients with
hepatic or renal dysfunction. In the randomized clinical trial,
patients were excluded for baseline serum bilirubin >1.5
mg/dL or baseline serum creatinine >2 mg/dL
• ABRAXANE can cause fetal harm when administered to a

pregnant woman. Women of childbearing potential should be
advised to avoid becoming pregnant while receiving
treatment with ABRAXANE
• Men should be advised to not father a child while receiving

treatment with ABRAXANE
Inc; May 2007.
Warnings (cont.)
• Albumin (human)
– ABRAXANE contains albumin (human), USP, a
derivative of human blood
– Pharmaceutical-grade human albumin has an
extremely remote risk of disease transmission
– No cases of transmission of viral disease or
Creutzfeldt-Jacob disease have ever been identified
for albumin
Inc; May 2007.
Precautions
• Hematology
– Patients should not be retreated with subsequent cycles of
ABRAXANE until neutrophils recover to a level >1,500 cells/mm3 and
platelets recover to a level >100,000 cells/mm3
• Nervous System
– Sensory neuropathy occurs frequently with ABRAXANE
– If grade 3 sensory neuropathy develops, treatment should be
withheld until resolution to grade 1 or 2 followed by a dose reduction
for all subsequent courses of ABRAXANE
• Cardiovascular
– Severe cardiovascular events possibly related to single-agent
ABRAXANE occurred in approximately 3% of patients in the
randomized study. These events included chest pain, cardiac arrest,
supraventricular tachycardia, edema, thrombosis, pulmonary
thromboembolism, pulmonary embolism, and hypertension
• Injection Site Reaction
– Reactions occur infrequently
Precautions (cont.)
• Drug Interactions
– No drugs have been studied with ABRAXANE
– Caution should be exercised when administering ABRAXANE
concomitantly with known substrates or inhibitors of CYP2C8 and
CYP3A4
• Pregnancy
– Pregnancy Category D
• Nursing Mothers
– It is recommended that nursing be discontinued when receiving
ABRAXANE therapy.
• Pediatric Use
– The safety and effectiveness of ABRAXANE in pediatric patients have
not been evaluated.
• Geriatric Use
– No toxicities occurred notably more frequently among elderly patients
who received ABRAXANE
Contraindications
• ABRAXANE should not be used in patients who have baseline
neutrophil counts of <1,500 cells/mm3
– It is recommended that frequent monitoring of blood cell

counts be performed on all patients receiving ABRAXANE until
neutrophils recover to a level >1,500 cells/mm3 and platelets
recover to a level >100,000 cells/mm3
– In the case of severe neutropenia (<500 cells/mm3 for 7 days

or more) during a course of ABRAXANE therapy, a dose
reduction for all subsequent courses of therapy is
recommended
Inc; May 2007.
Important Safety Information

• In the randomized metastatic breast cancer study, the most important
adverse events included neutropenia (all cases 80%; severe 9%),
anemia (all 33%; severe 1%), infections (24%), sensory neuropathy
(any symptoms 71%; severe 10%), nausea (any 30%; severe 3%),
vomiting (any 18%; severe 4%), diarrhea (any 27%; severe <1%),
myalgia/arthralgia (any 44%; severe 8%), and mucositis (any 7%;
severe <1%)
• Other adverse reactions included asthenia (any 47%; severe 8%),

ocular/visual disturbances (any 13%; severe 1%), fluid retention (any
10%; severe 0%), alopecia (90%), hepatic dysfunction (elevations in
bilirubin 7%, alkaline phosphatase 36%, AST [SGOT] 39%), and
renal dysfunction (any 11%; severe 1%)
Inc; May 2007.
Important Safety Information (cont.)

• Thrombocytopenia (any 2%; severe <1%), hypersensitivity
reactions (any 4%; severe 0%), cardiovascular reactions
(severe 3%), and injection site reactions (<1%) were
uncommon
• During postmarketing surveillance, rare occurrences of severe

hypersensitivity reactions have been reported with ABRAXANE
Inc; May 2007.
ABRAXANE
Dosing and Administration

ABRAXANE Dose
260 mg/m2 IV over 30

minutes every 3 weeks
Inc; May 2007.
ABRAXANE Dose (cont.)

• ABRAXANE dose
– It is recommended that ABRAXANE be infused over 30
minutes at a dose of 260 mg/m2 every 3 weeks
• Criteria for dose reduction
– ANC <500 cells/mm3 for a week or longer: resume treatment
with a reduced dose when ANC >1500 cells/mm3
– Severe sensory neuropathy: resume treatment with reduced
dose when neuropathy improves to grade 1 or 2
• Levels of dose reduction
– First toxicity occurrence = 220 mg/m2 for all subsequent
courses
– Second toxicity occurrence = 180 mg/m2 for all subsequent
courses
Inc; May 2007.
Preparation for Administration

Safety first Wear gloves
Reconstitute Aseptically, reconstitute each vial of ABRAXANE by injecting 20

mL of 0.9% sodium chloride injection, USP over a minimum of
1 minute onto the INSIDE WALL OF THE VIAL
DO NOT INJECT SOLUTION ONTO THE LYOPHILIZED CAKE
Let Stand Allow vial to sit for a minimum of 5 minutes
Swirl Gently swirl or invert vial slowly for at least 2 minutes until
cake/powder dissolves completely
AVOID GENERATING FOAM, which will delay reconstitution
Inject into IV bag Inject reconstituted ABRAXANE into an empty, sterile, IV bag
(PVC container, PVC or non-PVC IV bag)
USE OF AN IN-LINE FILTER IS NOT RECOMMENDED
Preparation for Administration (cont.)

• Each mL reconstituted ABRAXANE will contain 5 mg/mL
of paclitaxel
• Calculate the exact total dosing volume of 5 mg/mL

suspension required for the patient
Dosing volume (mL) = total dose (mg) / 5 mg/mL
Inc; May 2007.
ABRAXANE
Summary
ABRAXANE Summary of Clinical Benefits
• Allows delivery of 49% higher dose of paclitaxel

• No premedication required for solvent-related
hypersensitivity reactions
• Infused over 30 minutes
Inc; May 2007.
ABRAXANE Summary of Clinical Benefits (cont.)
• Nearly double the reconciled target lesion response rate

– All randomized patients
• ABRAXANE (n=233): 21.5% (CI: 16.19% - 26.73%)
• Solvent-based p=0.003
paclitaxel (n=227): 11.1% (CI: 6.94% - 15.09%)
– Patients who had failed combination chemotherapy or

relapsed within 6 months of adjuvant chemotherapy
• ABRAXANE (n=129): 15.5% (CI: 9.26% - 21.75%)

• Solvent-based p=NS
paclitaxel (n=143): 8.4% (CI: 3.85% - 12.94%)
Inc; May 2007.
ABRAXANE Tolerability Summary

• Lower incidence of grade 4 neutropenia: 9% in the ABRAXANE group
vs 22% in the solvent-based paclitaxel group1
• 10% of patients in the ABRAXANE arm developed grade 3 sensory
neuropathy vs 2% of patients in the solvent-based paclitaxel arm1
– 58% of ABRAXANE-treated patients with grade 3 sensory
neuropathy had improvement to grade 2 or less within a median
of 22 days, often allowing resumption of therapy at a reduced
dose1
• 3% of patients discontinued ABRAXANE due to sensory neuropathy
of any grade vs <1% in the solvent-based paclitaxel arm2
• No toxicities occurred notably more frequently among elderly patients1
1
Inc; May 2007.
2
Data on file, DA-ABR-02, Abraxis BioScience, Inc.
Abraxis Oncology and AstraZeneca

Clinical Forum
Questions
Abraxis Oncology is a division of Abraxis BioScience, Inc. All Abraxis BioScience, Inc. corporate names, names
of services, and names of products referred to herein are trade names, service marks and/or trademarks that
are owned by or licensed to Abraxis BioScience, its divisions, or its affiliates, unless otherwise noted.
ABRAXANE is marketed under a co-promotion agreement between Abraxis BioScience, Inc. and AstraZeneca.
Copyright © 2007 Abraxis BioScience, Inc. and AstraZeneca Pharmaceuticals LP. All Rights Reserved.
References
Inc; May 2007.
Gelderblom H, Verweij J, Nooter K, et al. Cremophor EL: the drawbacks and advantages of vehicle selection for
drug formulation. Eur J Cancer. 2001;37:1590-1598.
Gradishar WJ, Tjulandin S, Davidson N, et al. Phase III trial of nanoparticle albumin-bound paclitaxel compared
with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005;23:7794-
7803.
Ibrahim NK, Desai N, Legha S, et al. Phase I and pharmacokinetic study of ABI-007, a cremophor-free, protein-
stabilized, nanoparticle formulation of paclitaxel. Clin Cancer Res. 2002;8:1038-1044.
Lorenz W, Schmal A, Schult H, et al. Histamine release and hypotensive reactions in dogs by solubilizing
agents and fatty acids: analysis of various components in cremophor EL and development of a compound
with reduced toxicity. Agents Actions. 1982;12:64-80.
Mielke S, Sparreboom A, Mross K. Peripheral neuropathy: a persisting challenge in paclitaxel-based regimens.
Eur J Cancer. 2006;42:24-30.
Nyman DW, Campbell KJ, Hersh E, et al. A phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle
formulation of paclitaxel in patients with advanced nonhematologic malignancies. J Clin Oncol.
2005;23:7785-7793.
References (con’t)
O’Shaughnessy J, Tjulandin S, Davidson N, et al. ABI-007 (ABRAXANE™), a nanoparticle albumin-bound
(nab) paclitaxel demonstrates superior efficacy vs Taxol® in metastatic breast cancer:
a phase III trial. Presented at: San Antonio Breast Cancer Symposium; December 3-6, 2003; San
Antonio, TX.
Scripture CD, Figg WD, Sparreboom A. Paclitaxel chemotherapy: from empiricism to a mechanism-based
formulation strategy. Ther Clin Risk Manag. 2005;1:107-114.
Sparreboom A, Scripture CD, Trieu V, et al. Comparative preclinical and clinical pharmacokinetics of a
cremophor-free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated in
cremophor (Taxol). Clin Cancer Res. 2005;11:4136-4143.
Sparreboom A, van Zuylen L, Brouwer E, et al. Cremophor EL-mediated alteration of paclitaxel distribution
in human blood: clinical pharmacokinetic Implications. Cancer Res. 1999;59:1454-1457.
Szebeni J, Muggia FM, Alving CR. Complement activation by cremophor EL as a possible contributor to
hypersensitivity to paclitaxel: an in vitro study. J Natl Cancer Inst. 1998;90:300-306.
Szebeni J, Alving CR, Savay S, et al. Formation of complement-activating particles in aqueous solutions of
taxol: possible role in hypersensitivity reactions. Int Immunopharmacol. 2001;1:721-735.
ten Tije AJ, Verweij J, Loos WJ, et al. Pharmacological effects of formulation vehicles: implications for
cancer chemotherapy. Clin Pharmacokinet. 2003;42:665-685.
Van Zuylen L, Verweij J, Sparreboom A. Role of formulation vehicles in taxane pharmacology. Invest New
Drugs. 2001;19:125-141.
Weiss RB, Donehower RC, Wiernik PH, et al. Hypersensitivity reactions from taxol. J Clin Oncol.
1990;8:1263-1268.
ABRAXANE
Backup Slides
To be used only in response to unsolicited
questions from the audience
Investigator Reported Response Rates

Investigator Reported Response Rates
(Phase III Study Publication)
45 ABRAXANE
40 Solvent-based
paclitaxel
35 33% p=0.001
30 27% p=0.006
25
20 19%
15 13%
10
st nei t a pf o e gat necr e P
0
n=229 n=225 n=132 n=136
All patients Second-line or greater therapy

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ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound)

Abraxis Oncology and AstraZeneca

Treatment in Metastatic Breast

ABRAXANE Presentation Overview

Limitations of Solvent-based Paclitaxel

• Conventional, solvent-based paclitaxel requires a

• CrEL has been implicated in adverse reactions seen with

• CrEL may alter the pharmacokinetics of paclitaxel

Impact of Cremophor® EL on Paclitaxel

Premedication with steroids

Cumulative peripheral sensory

ten Tije et al. Clin Pharmacokinet. 2003;42:665-685.

ABRAXANE Product Description

ABRAXANE has Linear Pharmacokinetics

Mean AUC vs ABRAXANE Doses Studied (infused over 30 minutes)2,3

ABRAXANE Dose (mg/m2)

ABRAXANE Clinical Experience

Phase III Trial Design

ABRAXANE 260 mg/m2

Solvent-based Paclitaxel 175 mg/m2

Gradishar et al. J Clin Oncol. 2005;23:7794-7803.

Gradishar et al. J Clin Oncol. 2005;23:7794-7803.

• 454 patients received at least one dose of drug1

Primary Site of Metastatic Disease

Gradishar et al. J Clin Oncol. 2005;23:7794-7803.

Anthracycline: adjuvant and/or metastatic 77% 78%

Gradishar et al. J Clin Oncol. 2005;23:7794-7803.

Mean cycles/patient 5.6 5.2

Mean dose/m2/cycle 255 mg 171 mg

Mean percentage of protocol dose 98% 98%

Mean total paclitaxel/patient/m2 1459 mg 909 mg

Median total paclitaxel/patient/m2 1560 mg 875 mg

Concomitant Medications: Percent of Cycles

5-HT3 antagonists 16% 14%

Any steroid medication 8% 98%

Steroids for HSR prophylaxis* 2% 95%

Colony-stimulating factors <1% 3%

Reconciled Target Lesion Response Rate

Nearly Doubled Response Rate

All randomized patients Patients who had failed combination

ABRAXANE Phase III Trial

Safety and Tolerability

Thrombocytopenia <1% 0% <1% 0% 0.387

Anemia <1% <1% 0% 0% 0.192

Febrile neutropenia <1% <1% <1% 0% 0.491

* During postmarketing surveillance, rare occurrences of severe hypersensitivity reactions

Time to Improvement of Grade 3 Neuropathy

ABRAXANE Median Time to Improvement: 22

0 10 20 30 40 50 60 70 80 90 100 110 120 130

Gradishar et al. J Clin Oncol. 2005;23:7794-7803.

Other Toxicity Results

Toxicity Results: Geriatric Use

• No toxicities occurred notably more frequently among the

• ABRAXANE can cause fetal harm when administered to a

• Men should be advised to not father a child while receiving

– It is recommended that frequent monitoring of blood cell

– In the case of severe neutropenia (<500 cells/mm3 for 7 days

Important Safety Information

• Other adverse reactions included asthenia (any 47%; severe 8%),

Important Safety Information (cont.)

• During postmarketing surveillance, rare occurrences of severe

Dosing and Administration