1. NDA 20-449 SE-011 Docetaxel FDA Review

2. FDA Review Team Biostatistics –Clara Chu, PhD. –Gang Chen, PhD. Biopharmaceutics –Safaa Ibrahim PhD –Atiq Rahman, PhD. Project Manager –Ann Staten, RD Medical –Julie Beitz, MD

3. Proposed Indication “for the treatment of patients with locally advanced or metastatic NSCLC after failure of prior chemotherapy”

4. The Randomized, Controlled Trials TAX 317 –Docetaxel 100 mg (N= 49) –Best Supportive Care (N=51)  –Docetaxel 75 mg (N=55) –Best Supportive Care (N=49) TAX 320 –Docetaxel 100 mg (N=125) –Docetaxel 75 mg (N=125) –Vinorelbine OR Ifosfamide (N=123)

5. Trials’ Shared Features Eligibility/Exclusion Criteria –prior platinum-based chemotherapy required in both studies –prior taxane exposure excluded in TAX 317 only Primary Endpoint = Survival Secondary Endpoints

6. Major Efficacy Issues Pre-specified vs. Other Analyses Consistency across studies

7. Survival - Prespecified Analyses

8. Survival - Retrospective Analyses

9. K-M Survival Curves - 75 mg vs. Control TAX 317 TAX 320 SurvIvIngSurvIvIng SurvIvIngSurvIvIng Tax BSC Tax Control

10. Rate of Survival at One Year - Retrospective Analyses

11. Historical Perspective ŸLack of phase 3 data in the second line setting ŸFirst line rates of survival at one year are reported in the range of 18 - 43% for combination regimens (in randomized controlled trials) äGemcitabine + Cisplatin = 39% äPactilaxel + Cisplatin = 36% äVinorelbine + Cisplatin = 35%

12. Survival: Summary of Review Issues A significant difference between arms was demonstrated in a pre-specified survival analysis in only one study (TAX317, pooled), in an updated analysis The analysis of overall survival at the 75 mg dose level favored docetaxel in a retrospective analysis of a single study (TAX317) Exploratory analyses of rates of one year survival favor docetaxel in both studies Rates of one year survival are comparable to those reported in the first line setting

13. Clinical Benefit Parameters

14. Safety

15. Summary Safety  QoL  Survival 