A probabilistic threshold analysis of metformin (Met) with enzalutamide (Enza) to determine the cost and added efficacy needed to make such a combination theray cost-effective (CE).

Abstract

e577 Background: Enza has become known for its' effectiveness in treating patients with metastatic castrate-resistant prostate cancer. However, Enza is expensive (~$3175/month) and unlikely to be CE at any willingness to pay (WTP) threshold from $0-$125 000/quality-adjusted life years (QALYs). Met is inexpensive (~$8.00/month) and recently two large population-based studies of prostate cancer (PCa) demonstrated that diabetics taking Met had improved PCa specific and overall survival compared to those not taking Met. As a result we theorized that there must be a cost of Enza and a specific added effect Met could provide that would make Met a CE adjuvant therapy to Enza even though it is not currently used as such. Methods: We constructed a Markov-based decision analytic model and performed a probabilistic threshold analysis to narrow in on several combinations of costs of Enza and added efficacies needed to make Enza + Met a CE combination therapy at different WTP thresholds. Costs, utilities, and transition probabilities were derived from existing literature. Effectiveness was measured using QALYs. Costs and QALYs were considered over a lifetime horizon and discounted at 5% per annum. Results: At a WTP threshold of $50 000/QALY Enza + Met is unlikely to be CE no matter the cost decrement or added efficacy applied to the model. At a WTP threshold of $75 000/QALY Met is also unlikely to be CE unless the price of Enza could drop to $1934/month and Met could also add 1% to the efficacy of Enza. At Enza's current cost and a WTP threshold of $100 000, Enza + Met could be CE barring Met adds 0.621% to the number of patients still on treatment at 36 months. Conclusions: Enza + Met is unlikely to be CE at WTP thresholds of $50 000/QALY or $75 000/QALY unless there is a significant price drop for Enza; these results make sense because a therapy that is considered not CE at these WTP thresholds by itself is unlikely to be CE with a theoretical adjuvant therapy that would hold a patient on such a treatment for even longer. Our results show that the only way for Enza + Met to be CE is through the theoretical overall survival benefit of Met as the price of Enza is unlikely to drop any time soon.