Lang, Daenielle K.

5583 Background: FDA has approved three novel AAs [Apalutamide(A), Darolutamide(D) and Enzalutamide(E)] in combination with Androgen deprivation therapy ( ADT) for treatment of (nmCRPC) patients (pts). We report the cost-effectiveness of these drugs from the US perspective to help facilitate the choice of these agents for clinical practice. Methods: A life time Markov state-transition model was constructed with three health states (Metastasis-Free Survival[MFS], Metastatic disease, and Death) to compare cost-effectiveness of AA therapies for treatment of nmCRPC based on US healthcare payer perspective. A network meta-analysis of MFS and OS was conducted due to the lack of head to head trials. An approximation of the original individual-level patient time-to-event data were derived from digitized Kaplan-Meier curves for OS and MFS. Weibull distributions was selected as the best fitted model fitted and extrapolated as per the NICE decision support unit recommendations. Medication costs were based on wholesale acquisition cost. Adverse event (AE) grades 3/4 management costs were incorporated in the model. Discount rate of 3% per year was applied to costs and effects. Life years (LYs) and quality adjusted life years (QALYs) for each treatment as well as the incremental cost effectiveness (ICER) and cost utility (ICUR) ratios were estimated. Base case analyses (BCA) and probabilistic sensitivity analyses (PSA) were estimated. Results: The table summarizes the results form BCA analyses. A+ADT offers best gain in LYs (8.37yrs) and QALYs (5.30 yrs) but at higher cost. Conclusions: Apalutamide was associated with gains in LYs and QALYs traded off with higher lifetime cost relative to other AA alternatives. ADT was associated with lower gains in LYs and QALYs traded off with lower lifetime cost relative to other alternatives. Based on a $150,000/QALY threshold pay off, A+ADT is likely more cost effective compared to E+ADT or ADT alone; while E+ ADT may be more cost effective compared to D+ ADT. [Table: see text]

335 Background: Network meta-analysis can provide useful evidence for relative efficacy and toxicity of different treatment options in absence of head-to-head trials. Previously, we reported no difference in efficacy between Apalutamide (APA) and Enzalutamide (ENZA). In this analysis, we provide updated indirect comparisons of all FDA approved agents (APA,ENZA, Darolutamide(DARO) for the treatment of M0CRPC with rapid PSA doubling time. Methods: MEDLINE, EMBASE and Cochrane Library were searched to identify relevant clinical trials. Hazard ratios (HR) and 95% confidence interval (CI) for Metastasis Free Survival (MFS), Overall Survival (OS) and data on grade 3 or higher AEs were abstracted. Bayesian network meta-analysis was conducted using WinBUGS 1.4.3 software (MRC Biostatistics Unit, Cambridge, UK) to perform an indirect comparisons. Risk for bias was assessed using the Cochrane Collaboration’s tool. Results: Three RCTs (SPARTAN, PROSPER and ARAMIS) compared APA, ENZA and DARO respectively in combination with ADT to ADT alone. A total of 4117 patients were included in efficacy analysis (2694 received novel hormonal agents and 1423 received ADT and placebo). There were no statistically significant differences in MFS (HR 0.97, 95% CrI 0.74 - 1.30) between APA and ENZA; however, both APA 0.69 (95% CI 0.52 -0.92) and ENZA 0.71 (95% CrI 0.53, 0.92) significantly improved MFS as compared to DARO. There were no statistically significant differences in OS between these drugs. DARO had fewer grade 3 or higher adverse events of fatigue (HR 0.09, 95% CrI 0.01 – 0.51) compared to ENZA. However other common adverse events such as hypertension, falls, coronary artery disease/myocardial infarction and diarrhea were not significantly different between treatment groups. There was low risk of bias amongst included studies. Conclusions: APNA and ENZA provide significant improved in MFS as compared to DARO in patients with M0CRPC. The drugs have similar toxicity profile except that DARO was associated with lower incidence of fatigue compared to ENZA. Cost effective analysis of these drugs will be reported separately.