NDA SE-011 Docetaxel FDA Review
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
Proposed Indication “for the treatment of patients with locally advanced or metastatic NSCLC after failure of prior chemotherapy”
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)
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
Major Efficacy Issues Pre-specified vs. Other Analyses Consistency across studies
Survival - Prespecified Analyses
Survival - Retrospective Analyses
K-M Survival Curves - 75 mg vs. Control TAX 317 TAX 320 SurvIvIngSurvIvIng SurvIvIngSurvIvIng Tax BSC Tax Control
Rate of Survival at One Year - Retrospective Analyses
Historical Perspective Lack of phase 3 data in the second line setting First line rates of survival at one year are reported in the range of % for combination regimens (in randomized controlled trials) äGemcitabine + Cisplatin = 39% äPactilaxel + Cisplatin = 36% äVinorelbine + Cisplatin = 35%
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
Clinical Benefit Parameters
Safety
Summary Safety QoL Survival