Randomized, open label, phase III trial of figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin in patients with non-small cell lung cancer (NSCLC).

Abstract

7500 Background: The Insulin-like growth factor type I receptor (IGF-IR) plays an important role in normal cellular growth and development and is implicated in the regulation of tumor growth. A phase III study was conducted to test the efficacy of the combination of paclitaxel, carboplatin, and figitumumab (CP-751871), a monoclonal antibody targeting the IGF-IR, as first-line treatment of advanced NSCLC. Methods: Eight hundred twenty pts were to be randomized 1:1 to receive paclitaxel (200 mg/m2), carboplatin (AUC = 6), and figitumumab (20 mg/Kg) (PCF) or paclitaxel and carboplatin alone (PC) q3weeks for up to 6 cycles. The primary study endpoint was overall survival (90% power, one sided 0.025 alpha, hazard ratio [HR] 0.77). Results: Accrual has been permanently suspended at 681 pts (median age 62 years, 77% male, 86% squamous cell carcinoma, 88% stage IV, 42% current smokers) enrolled based on a planned interim analysis at 225 events with a HR that crossed the prespecified futility boundary of 1.1 favoring PC. Serious adverse events in the PCF arm included dehydration, hyperglycemia, and hemoptysis. The potential relationship with early death (within 42 days of randomization) of a series of clinical and laboratory parameters was investigated. Low pre-treatment body mass index (p = 0.003) and creatinine clearance (p = 0.1) were predictive of early death for patients receiving figitumumab. Furthermore, PFC/PC survival HR estimates favored PC in pts with low baseline IGF-1 (minimum p = 0.006 for IGF1 < 120 ng/mL; HR 1.6) and PCF in those with high baseline IGF-1 (minimum p = 0.13 for IGF1 > 145 ng/mL; HR = 0.62). Conclusions: Potential subsets of pts with differential safety and efficacy profiles on figitumumab treatment were identified. Additional analyses will be submitted as a late breaking abstract. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer