Second Japan-SWOG common arm analysis of paclitaxel/carboplatin in advanced stage non-small cell lung cancer (NSCLC): A model for testing population-related pharmacogenomics

Abstract

7050 Background: Whether results of clinical trials performed outside the United States (US) can be fully extrapolated to US populations remains in question due to potential differences in trial designs, study-specific criteria, patient demographics, and population-related pharmacogenomics. The first of these comparisons, FACS-S0003 has been presented (Gandara, PASCO, 2004). Here we present the second comparative analysis. Methods: We prospectively designed & conducted 3 separate phase III trials in advanced NSCLC linked by a “common arm” with identical eligibility, staging, response & toxicity criteria, to: 1) determine similarities & differences in patient demographics & outcomes in cooperative group trials in Japan (in this analysis, the Japan Multinational Trial Organization LC03) & the US (SWOG 0003), 2) provide the basis for global standardization in clinical trials in NSCLC, and 3) facilitate regulatory changes needed for joint Japan-US studies. We performed a planned comparative analysis of the paclitaxel/carboplatin arms from LC03 & S0003, which had identical doses and schedules of paclitaxel dose (225mg/m2) and carboplatin (AUC 6). Conclusions: 1) This common arm analysis, as in our prior FACS-S003 report, shows great similarities in patient demographics between the LC03 and S0003. 2) Variable toxicities may be due to population-related pharmacogenomics (increased neutropenia & febrile neutropenia in LC03), and could be explained by polymorphisms in cytochrome P450 for paclitaxel metabolism (ongoing analysis). 3) Survival is increased in LC03. 4) Future joint Japan-US clinical trials should assess possible pharmacogenomic differences in drug disposition. [Table: see text] No significant financial relationships to disclose.