# Presentation: 684859

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

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

**In Metastatic Breast Cancer Abraxane Has Greater Anti-tumor Activity Than Taxol**

## Removal of Cremophor Resulted in Superior Anti-tumor and Intratumor Paclitaxel Concentrations in Preclinical Models

## Preclinical Finding:  Replacing Cremophor with Albumin Enhanced the Efficacy of Paclitaxel in Breast Cancer

**Athymic mice with human xenografts  (n = 10 per group; daily administration for 5 days)**

**Breast MX-1 tumor model**
**equidose paclitaxel comparison**

**Preclinical Finding:  ****Replacing Cremophor with Albumin Enhanced the Efficacy of Paclitaxel in Breast Cancer**

## Abraxane Results in Higher Intra-tumoral Concentration of Paclitaxel Compared to Taxol 

**Abraxane Results in Higher Intra-tumoral Concentration of Paclitaxel Compared to Taxol **

**ABI-007 = 1.33 X Taxol**

**Desai et al. Clin Can Res, 2006.**

**Intratumor paclitaxel levels following equal doses ABI-007 and Taxol in nude mice bearing MX-1 human breast cancer xenografts**

## Preclinical Superiority of Abraxane over Taxol: Anti-tumor Activity Predicted Results in the Clinic

**Prostate**** PC3 (equitoxic dose comparison)**

**Ovarian ****SKOV3 (equitoxic dose comparison)**

**Desai N, et al. Clin Cancer Res 2006;12(4), 1317-24**

**Athymic mice with human xenografts  (n = 10 per group; daily administration for 5 days)**

**Preclinical Superiority of Abraxane over Taxol: ****Anti-tumor Activity Predicted Results in the Clinic**

**Colon HT29**** (equitoxic dose comparison)**

## Abraxane vs. TaxolPhase 3 Clinical Trial

**Journal Clin Oncology, 2005;23.**

## Phase 3 Trial Design

**Randomization (1:1)****N = 460**

**Taxol 175 mg/m****2****IV over 3 hrs q 3 wk**
**Standard Premedication with Dexamethasone and Anti-histamines**

**Abraxane 260 mg/m2**** ****IV over 30 min q 3 wk**
**No Standard Premedication**

## Investigator Response DemonstratingSuperior Efficacy Across All Lines of Therapyin Metastatic Breast Cancer

**Replacement of Cremophor with albumin enhanced the efficacy of paclitaxel in metastatic breast cancer**

**Source:  Abraxane NDA**

## Response Assessment Demonstrated Superiority of Cremophor-free Paclitaxel Independent of Dataset and Reviewer

**Source:  Abraxane NDA**

## Abraxane Response Rate (Package Insert) Statistically Significantly Higher than Taxol 

**Source:  Abraxane Package Insert**

## Prolonged Time to Disease ProgressionIndependent Radiology Laboratory Response Dataset, Investigator Response Dataset, and Follow-up Disease Progression Data

**Note: *****P*****-value from log-rank test.**
**Source:  NDA Labeling Supplement**

**Abraxane (N = 233)**
**Taxol (N = 227)**
***P*****-value = 0.002**
**Hazard Ratio = 0.721**

**Proportion of no Progression**

## No Difference in Overall SurvivalAll Patients

**Proportion of no Progression**

**Abraxane (N = 129)**
**Taxol (N = 143)**
***P*****-value = 0.348**
**Hazard Ratio = 0.904**

**Note: *****P*****-value from log-rank test.**
**Source:  NDA Labeling Supplement**

## Second Phase 3 Randomized Controlled Clinical Trial Confirms the Results from CA012

|               | Abraxane260 mg/m2 | Taxol175 mg/m2 | P-value |
| --- | --- | --- | --- |
| Patients Evaluable (All) | N = 81 | N = 82 | 0.025 |
|          Response Rate | 38% | 21% |  |
| Patients Evaluable (First Line) | N = 47 | N = 48 | 0.005 |
|          Response Rate | 47% | 19% |  |

**GCP study required by the Chinese Regulatory Authorities for Approval of Abraxane in China****(PI:Guan Zhong-Zen)**
**100 Patients per arm (Abraxane vs. Taxol)**
**Dose: Abraxane 260 mg/m****2****, Taxol 175 mg/m****2**** q3w**

## Preliminary Progression-Free SurvivalPer-Protocol Population (Study CA201)

**Abraxane 260 mg/m****2**** (N = 94)**
**Taxol 175 mg/m****2**** (N = 93)**
***P*****-value = 0.090**
**HR = 0.644**

**Proportion Not Progressed**

**33% of events**

## Hypotheses for Increased Anti-tumor Activity

**A Combination of Two Factors**

## Summary: Abraxane is Efficacious and Well Tolerated at a Higher Paclitaxel Dose 

**Abraxane consistently demonstrated superior****anti-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**