Duration of adjuvant immunotherapy-biologic, clinical and economic considerations.

The financial impact of an extensive duration of adjuvant immunotherapy is severe. The clinical and biological rationale for this extensive duration is unclear. This study aims to understand the biologic and clinical rationale for the duration of treatment in designing adjuvant trials and to assess the economic impact of different treatment durations in adjuvant therapy. We searched http://www.clinicaltrials.gov for adjuvant immunotherapy clinical trials. Based on our inclusion and exclusion criteria, we identified 47 trials targeting PD-1, PD-L1, and CTLA-4. We examined the duration of these trials and performed a US based budget impact analysis of three representative trials based on various data sources. Most current adjuvant immunotherapy trials provide treatment for 1 year. Our budget impact analyses estimate that the cost per patient of 1 year treatment with nivolumab for melanoma is $165,000 while the cost of 3 years treatment with ipilimumab for melanoma is more than $1,850,000 assuming full duration of treatment. The annual cost for adjuvant treatment with nivolumab for melanoma is approximately $1.15 billion for the entire target population in the United States assuming full uptake. The necessary duration of adjuvant immunotherapy is unknown. The rationale for duration in current trials is not clear and may be longer than necessary. Non-inferiority trials testing shorter duration of therapies should be conducted. Appropriate mechanisms to fund such trials should be sought out by healthcare payers.