Japan-SWOG common arm analysis of paclitaxel/carboplatin in advanced stage non-small cell lung cancer (NSCLC): A model for prospective comparison of cooperative group trials

Abstract

7007 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. Methods: We prospectively designed & conducted 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 (Four Arm Cooperative Study or FACS) & 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 sponsored by the US National Cancer Institute (NCI). We performed a planned comparative analysis of the paclitaxel/carboplatin arms from FACS & S0003, identical except for paclitaxel dose of 200mg/m2 in FACS, 225mg/m2 in S0003, based on the MTD from separate phase I studies in Japan and the US. Carboplatin: AUC 6 in both. Results: Conclusions: 1) This common arm analysis shows great similarities in patient demographics between the FACS and S0003. 2) Variable toxicities may be due to differences in cumulative paclitaxel dose (neuropathy) and/or population-related pharmacogenomics (increased neutropenia & febrile neutropenia in FACS despite lower paclitaxel dose). 3) Survival is increased in FACS. 4) Future joint Japan-US clinical trials should consider possible pharmacogenomic differences in drug disposition. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb