Results of the Phase 3 Clinical Trials of Abraxane vs. Taxol in Metastatic Breast Cancer

1
Results of the Phase 3 Clinical Trials of
Abraxane vs. Taxol in Metastatic Breast Cancer
In Metastatic Breast Cancer Abraxane Has Greater
Anti-tumor Activity Than Taxol

• William J. Gradishar, MD, FACP
• Professor of Medicine
• Northwestern University

2
Removal of Cremophor Resulted in Superior
Anti-tumor and Intratumor Paclitaxel
Concentrations in Preclinical Models
3
Preclinical Finding Replacing Cremophor with
Albumin Enhanced the Efficacy of Paclitaxel in
Breast Cancer
Breast MX-1 tumor model equidose paclitaxel
comparison
Athymic mice with human xenografts (n 10 per
group daily administration for 5 days)
Desai N, et al. Clin Cancer Res 200612(4),
1317-24
4
Abraxane Results in Higher Intra-tumoral
Concentration of Paclitaxel Compared to Taxol
Intratumor paclitaxel levels following equal
doses ABI-007 and Taxol in nude mice bearing MX-1
human breast cancer xenografts
ABI-007 1.33 X Taxol
Desai et al. Clin Can Res, 2006.
5
Preclinical Superiority of Abraxane over Taxol
Anti-tumor Activity Predicted Results in the
Clinic
Athymic mice with human xenografts (n 10 per
group daily administration for 5 days)
Lung H522 (equitoxic dose comparison)
Colon HT29 (equitoxic dose comparison)
Ovarian SKOV3 (equitoxic dose comparison)
Prostate PC3 (equitoxic dose comparison)
Desai N, et al. Clin Cancer Res 200612(4),
1317-24
6
Abraxane vs. TaxolPhase 3 Clinical Trial
Journal Clin Oncology, 200523.
7
Phase 3 Trial Design
Abraxane 260 mg/m2 IV over 30 min q 3 wk No
Standard Premedication
Randomization (11)N 460
Taxol 175 mg/m2IV over 3 hrs q 3 wk Standard
Premedication with Dexamethasone and
Anti-histamines
8
Investigator Response DemonstratingSuperior
Efficacy Across All Lines of Therapyin
Metastatic Breast Cancer
Replacement of Cremophor with albumin enhanced
the efficacy of paclitaxel in metastatic breast
cancer
Source Abraxane NDA
9
Response Assessment Demonstrated Superiority of
Cremophor-free Paclitaxel Independent of Dataset
and Reviewer
Source Abraxane NDA
10
Abraxane Response Rate (Package Insert)
Statistically Significantly Higher than Taxol
Source Abraxane Package Insert
11
Prolonged Time to Disease ProgressionIndependent
Radiology Laboratory Response Dataset,
Investigator Response Dataset, and Follow-up
Disease Progression Data
Abraxane (N 233) Taxol (N 227) P-value
0.002 Hazard Ratio 0.721
Proportion of no Progression
Note P-value from log-rank test. Source NDA
Labeling Supplement
12
No Difference in Overall SurvivalAll Patients
Abraxane (N 129) Taxol (N 143) P-value
0.348 Hazard Ratio 0.904
Proportion of no Progression
Note P-value from log-rank test. Source NDA
Labeling Supplement
13
Second Phase 3 Randomized Controlled Clinical
Trial Confirms the Results from CA012

• GCP study required by the Chinese Regulatory
  Authorities for Approval of Abraxane in
  China(PIGuan Zhong-Zen)
• 100 Patients per arm (Abraxane vs. Taxol)
• Dose Abraxane 260 mg/m2, Taxol 175 mg/m2 q3w

Abraxane260 mg/m2 Taxol175 mg/m2 P-value
Patients Evaluable (All) N 81 N 82 0.025
Response Rate 38 21 0.025
Patients Evaluable (First Line) N 47 N 48 0.005
Response Rate 47 19 0.005
14
Preliminary Progression-Free SurvivalPer-Protocol
Population (Study CA201)
Abraxane 260 mg/m2 (N 94) Taxol 175 mg/m2 (N
93) P-value 0.090 HR 0.644
Proportion Not Progressed
33 of events
15
Hypotheses for Increased Anti-tumor Activity
A Combination of Two Factors
16
Summary Abraxane is Efficacious and Well
Tolerated at a Higher Paclitaxel Dose

• Abraxane consistently demonstrated
  superioranti-tumor activity compared to Taxol in
  metastatic breast cancer
• There is no scientific reason to believe that
  Abraxane would be less effective in the adjuvant
  setting