Metformin (Met): A cost-effective adjunct therapy with enzalutamide (Enza) for metastatic castrate-resistant prostate cancer (mCRPC)?

340 Background: Several new therapies have changed the landscape of prostate cancer (PCa) treatment, primarily due to their effectiveness in treating patients with mCRPC. Enza has garnered much attention, but is relatively expensive (~$3175/month). Met is less expensive (~$8.00/month) and has been used for decades to treat patients with non-insulin dependent diabetes. Two recent large population-based studies of PCa have demonstrated that diabetics taking Met had improved PCa specific and overall survival compared to those not taking Met. As a result, we hypothesized that Met has the potential to be a cost-effective adjunct therapy to Enza, although it is not currently used as such. Methods: We constructed a Markov-based decision analytic model to compare the cost-effectiveness of Enza alone versus Enza combined with Met. Through expert elicitation, we assumed that adding Met to Enza increases its efficacy by 15%. All other costs, utilities, and transition probabilities were derived from existing literature or expert elicitation. Effectiveness was measured using quality-adjusted life years (QALYs). Costs and QALYs were considered over a lifetime horizon and discounted at 5% per annum. Cost-effectiveness was considered using a willingness to pay threshold of $50 000/QALY. Results: Adding Met to Enza increases expected lifetime costs per patient by $83 651, and improves the expected effectiveness of treatment by 3.74 QALYs, compared to Enza alone. The incremental cost-effectiveness ratio is $22 374/QALY. Accounting for parameter uncertainty, adding Met to Enza has a 72% probability of being cost-effective. Conclusions: Although Met is not currently used as an adjunct therapy to Enza, doing so would likely be cost-effective provided it is as effective as we have assumed in our model. Additionally, our results indicate that the combination of Enza and Met could be among the most cost effective interventions in oncology. However, given the uncertainty around the effectiveness of such an adjunct therapy, our results support the need for further clinical trials to provide more robust evidence of the effectiveness of such a combination therapy in clinical practice.