Figure 6.

Efficacy of ganitumab in combination with chemotherapeutic agents. A, multiple drug effect analyses were performed to determine the nature of interactions between ganitumab and chemotherapeutic agents commonly used for the treatment of primary and recurrent ovarian cancer. Combination index values were derived from variables of the median effect plots, and statistical tests were applied to determine whether the mean combination values at multiple effect levels (IC₂₀–IC₈₀) were significantly different from 1.0. In this analysis, synergy was defined as combination index values significantly lower than 1.0, antagonism as combination index values significantly higher than 1.0, and additivity as combination index values equal to 1.0. B, mice bearing about 200 mm³ OV-90 or (C) OVCAR-3 xenografts were randomly assigned into 4 treatment groups and treated intraperitoneally twice per week with ganitumab (300 µg/dose), hIgG1 (300 µg/dose), cisplatin (2.5 or 4.0 mg/kg), or a combination of ganitumab plus cisplatin: (OV-90, 30 µg/dose + 4.0 mg/kg; OV-CAR-3, 300 µg/dose + 2.5 mg/kg). Tumor volumes were measured twice per week using calipers. Data, mean volume ± SEM. B and C, ganitumab significantly enhanced the efficacy of cisplatin in the OV-90 (*, P < 0.001, 30 mg/dose ganitumab + 4.0 mg/kg cisplatin) and OVCAR-3 (*, P < 0.001, 300 mg/dose ganitumab + 2.5 mg/ kg cisplatin) tumor models.