Impact of Dose Delays and Alternative Dosing Regimens on Pertuzumab Pharmacokinetics.

PERJETA (pertuzumab), administered with Herceptin (trastuzumab), is used in the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Pertuzumab is currently approved with an initial loading dose of 840 mg, followed by a 420 mg maintenance dose IV every 3 weeks (Q3W). A re-loading dose is required if there's a 6-week or greater delay in treatment. In response to the potential treatment disruption due to COVID-19, the impact of dose delays and alternative dosing regimens on pertuzumab IV for HER2-positive breast cancer treatment is presented. Simulations were conducted by using the validated population pharmacokinetic model for pertuzumab, and included (1) 4, 6, and 9 week dose delays of the 840 mg/420 mg Q3W dosing regimen and (2) 840 mg/420 mg Q4W and 840 mg Q6W alternative dosing regimens. Simulations were compared to the currently approved pertuzumab dosing regimen. The simulations in 1000 virtual patients showed that a dose re-load (840 mg) is required following a dose delay of 6 weeks or greater to maintain comparable Ctrough levels to clinical trials. The 840 mg/420 mg Q4W and 840 mg Q6W alternative dosing regimens decrease median steady-state Ctrough by ∼40% compared to the approved regimen, and <90% of patients will be above the target Ctrough . Thus, the alternative 840 mg/420 mg Q4W and 840 mg Q6W pertuzumab dosing regimens are not recommended. Flexibility for IV PERJETA-based regimens is available with an alternative route of pertuzumab administration (subcutaneous vs intravenous). This article is protected by copyright. All rights reserved.