Dose Optimization of Immune Checkpoint Inhibitors: A Policy opportunity to reduce costs and improve access to immunotherapy in the United States.

BACKGROUND

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but are associated with high costs and limited accessibility. Optimizing dosing strategy to achieve a Pharmacokinetics/Pharmacodynamics (PK/PD) supported alternative lower dose (PPALD) that maintains clinical benefit and offers a cost-minimization strategy with substantial health system savings.

METHODS

We conducted a literature review of Phase 1/2 trials describing the PPALD dose of three commonly used ICIs: Pembrolizumab, Nivolumab and Atezolizumab. Alternate dosing strategies based on data for pembrolizumab (2mg/kg), nivolumab (2mg/kg) and atezolizumab (10mg/kg) were proposed. Public CMS Medicare Part B data on expenditure for these therapies was used to obtain average cost/dose, mg/dose, and number of Medicare beneficiaries between 2018-2021. Costs were calculated based on current FDA approved dosing and alternate dosing strategies.

RESULTS

PPALD resulted in substantially lower drug costs per patient for an 80kg individual compared with fixed dosing: pembrolizumab ($7,393.60 vs $9,242.00), nivolumab ($4,153.60 vs $12,460.80), and atezolizumab ($5,744.00 vs $8,616.00). Estimated 2018-2021 Medicare savings based on beneficiaries were $382.2 million for pembrolizumab, $943.1 million for nivolumab, and $114.4 million for atezolizumab, totaling nearly $1.44 billion.

CONCLUSION

Alternate immunotherapy dosing represents a high-value cost saving strategy to reduce health care costs and improve global access. Implementation requires regulatory adaptation, smaller vials, or vial-sharing to minimize waste.

POLICY SUMMARY: This policy analysis demonstrates that evidence-based alternate dosing of commonly used checkpoint inhibitors (Pembrolizumab, Nivolumab and Atezolizumab) could substantially reduce drug expenses while maintaining efficacy. Using Medicare Part B utilization data, we estimated that implementation of these alternative dosing strategies can help save over $1.44 billion between 2018-2021. These findings have important implications for health policy by improving patient access to immunotherapy and curtailing financial toxicity. This can be further facilitated by the support of policymakers, regulatory agencies supporting prospective validation studies and development of reimbursement models that encourage dose optimization.