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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. 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.

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

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

  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 2006;12(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 2006;12(4), 1317-24

  6. Abraxane vs. TaxolPhase 3 Clinical Trial Journal Clin Oncology, 2005;23.

  7. Phase 3 Trial Design Abraxane 260 mg/m2IV over 30 min q 3 wk No Standard Premedication Randomization (1:1)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. Reconciled Target Lesion Response Rate Investigator Target Lesion Response Rate Blinded Radiologist Target Lesion Response Rate 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(PI:Guan Zhong-Zen) • 100 Patients per arm (Abraxane vs. Taxol) • Dose: Abraxane 260 mg/m2, Taxol 175 mg/m2 q3w

  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. 50% higher paclitaxel dose 33% higher intra-tumor paclitaxel 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

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