Cost-effectiveness analysis of platinum-based chemotherapy treatment options for germline BRCA-mutated locally advanced/borderline resectable pancreatic cancer.

Abstract

e16246 Background: Patients with germline BRCA1/2 mutations (gBRCAm) have an increased risk for pancreatic ductal adenocarcinoma (PDAC). The NCCN 2020 guidelines recommend platinum-based chemotherapy (FOLFIRINOX or gemcitabine plus cisplatin) in patients with gBRCAm diagnosed with borderline resectable or locally advanced (BR/LA) PDAC; for patients without progression on chemotherapy, maintenance therapy with a PAPR inhibitor (PARPi) can be considered. FOLFIRINOX and gemcitabine plus cisplatin (GemCis), with or without maintenance PARPi, have not been directly compared in this patient population. The purpose of our study was to compare treatment outcomes, toxicity, costs, and quality-of-life of the two recommended platinum-based regimens, with or without maintenance PARPi (olaparib or veliparib), in patients with gBRCAm and BR/LA PDAC. Methods: We developed a decision-analytic mathematical model comparing the total cost and health outcomes of FOLFIRINOX, FOLFIRINOX + olaparib (FOLFIRNOX-O), GemCis, and GemCis + veliparib (GCV) over twelve years. The inputs for the model were estimated using clinical trial data and published literature. Natural history was used as a comparator. The primary endpoint was incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay (WTP) threshold of $100,000 per quality-adjusted-life-year (QALY). Secondary endpoints included overall survival (OS), progression-free survival (PFS), life-years (LYs) and total cost of care (USD). Results: Both FOLFIRINOX strategies were dominated by the GemCis strategies and thus eliminated from the efficiency frontier. GCV was the strategy that yielded the most life-years (2.05 LYs) but the ICER of $629,697.46 for this regimen far exceeded the WTP threshold. Therefore, GemCis was the cost-effective strategy, totaling incremental QALYs of 1.31 at a cost of $61,228.40 per QALY when compared to natural history. A one-way sensitivity analysis found that the GCV becomes the cost-effective strategy when the cost of maintenance PARPi is lowered to 4% of the base case. Conclusions: Our model found that GemCis is the cost-effective option for patients with gBRCAm and BR/LA PDAC. Neither of the strategies with maintenance PARPi were cost-effective. Additional clinical trial data with adequate follow-up are needed to confirm our findings.[Table: see text]