OBJECTIVES: Pancreatic cancer is predicted to be the second highest cause of cancer-related death by 2030 in the US. Based on significant improvement in overall survival, the FDA approved irinotecan liposome injection (nal-IRI, ONIVYDE^®), in combination with fluorouracil and leucovorin (5-FU/LV), to treat patients with metastatic pancreatic cancer (mPC) previously treated with gemcitabine-based chemotherapy. The objective of this research was to estimate the budget impact (BI) of adopting nal-IRI for a U.S. commercial payer. METHODS: Epidemiologic data, including SEER incidence rates, were used to estimate the total number of patients with pancreatic cancer in a hypothetical 1,000,000 member U.S. health plan. The fraction of these who have the metastatic form of pancreatic cancer, have been exposed to gemcitabine, are still seeking treatment, and receive nal-IRI was estimated based on a claims analysis and expert input. Eligible patients were assumed to be treated with one of the following: gemcitabine only, gemcitabine plus nab-paclitaxel, other gemcitabine-based regimen, FOLFIRINOX, FOLFOX, capecitabine, or nal-IRI plus 5-FU/LV. Cost of medicines were obtained from CMS ASP pricing files; administration and monitoring from the CMS physician fee schedule; adverse events from the claims analysis, except for nal-IRI where it was estimated. The incremental aggregate BI and per-member-per-month (PMPM) impacts were calculated. Given the high mortality of pancreatic cancer, later lines of therapy were not considered. RESULTS: A million-member commercial plan with average demographics, but no seniors, was estimated to have 52 members/year with pancreatic cancer of which 15 would be eligible for nal-IRI, and of which 3 would get the drug. Total incremental annual cost was estimated to be $74,629 or $0.006 PMPM. CONCLUSIONS: The survival benefits of nal-IRI plus 5-FU/LV as a treatment option for patients with pancreatic cancer is associated with a PMPM of $0.006, a modest increment due to cost offsets.