Challenges in Developing a Validated Biomarker for Angiogenesis Inhibitors: The Motesanib Experience

摘要: Purpose: We sought to develop placental growth factor as a predictive pharmacodynamic biomarker for motesanib efficacy first-line therapy in patients with advanced nonsquamous non–small-cell lung cancer. Experimental Design: Placental was evaluated at baseline and study week 4 (after 3 weeks treatment) an exploratory analysis of data from randomized phase 2 125 mg once daily plus carboplatin/paclitaxel prespecified randomized, double-blind vs placebo (MONET1). Associations between fold-change overall survival were using Cox proportional hazards models. Results: In the study, serum increased mean 2.8-fold 4. Patients $2.2-fold change (n=18) had significantly longer than those ,2.2-fold (n=19; 22.9 7.9 months; hazard ratio, 0.30; 95% CI, 0.12–0.74; P=0.009). Consequently, investigated MONET1 study. There no association log-transformed (continuous variable) (hazard 0.98; 0.79–1.22; P=0.868). did not meet its primary endpoint survival. Likewise, median similar among $2.0-fold (n=229) compared ,2.0-fold (n=127; 14.8 13.8 0.88; 0.67–1.15, P=0.340). Conclusions: Our results illustrate challenges successfully translating into studies. Trial Registration: ClinicalTrials.gov NCT00460317, NCT00369070