Dose Regimen Rationale for Panitumumab in Cancer Patients: To Be Based on Body Weight or Not

INTRODUCTION: Body weight can affect exposure, safety and efficacy of antibody-based therapies; sometimes these effects may not be clinically relevant. Panitumumab is approved for wild-type RAS metastatic colorectal cancer, using a body weight–based dosing regimen. Recently, a report cited fixed-dose usage of panitumumab, rather than approved body weight–based dosing. The current work evaluates optimal dosing regimen scientifically based on clinical data, modeling and simulation. Herein, we assessed the effect of fixed and body weight–based dosing on panitumumab pharmacokinetics to determine which approach resulted in the least interpatient pharmacokinetic variability. PATIENTS AND METHODS: From the Vectibix program, 352 patients enrolled in three studies were evaluated; they had received panitumumab (body weight–based dose: 6 mg/kg every 2 weeks) and had pharmacokinetic (maximum serum [C(max]) and trough [C(min)] concentrations) and body weight data available. Additionally, concentration-time profiles at fixed (480 mg) and body weight–based doses (6 mg/kg) were simulated using a population pharmacokinetics model developed from 1200 patients. RESULTS: After administration of panitumumab 6 mg/kg, C(max) and C(min) increased with increasing body weight; the mean C(max) and C(min) for patients weighing <65 kg (lower quartile) were 23% and 30% lower, respectively, than for those weighing >88 kg (upper quartile). The simulated area under the concentration–time curve (AUC) data also indicated that overall panitumumab exposure increased with increasing body weight for the body weight–based regimen. When AUC was simulated for a fixed dose (480 mg), the opposite effect was observed. Over the range of body weights, interpatient variability in simulated AUC was lower for the weight-based dose (29%) than for the fixed dose (34%). CONCLUSION: Results demonstrate that the weight-based dose (6 mg/kg) reduced variability in panitumumab exposure across the range of body weights compared with the fixed-dose approach, indicating that a body weight–based approach is the recommended patient dosing strategy.