Cost-effectiveness of radium-223 compared to best standard of care, abiraterone acetate and enzalutamide in the treatment of castration resistant prostate cancer in the Netherlands

Background: The treatment landscape of metastatic castration resistant prostate cancer (mCRPC) has changed with the introduction of abiraterone acetate (AA), enzalutamide (EN) and radium-223 (Ra-223). Little is known about the cost-effectiveness of these novel agents. This study investigates the cost-effectiveness of Ra-223 in the Netherlands. First, the costeffectiveness of Ra-223 will be evaluated against best supportive care (BSoC) in the mCRPC population. Second, the cost-effectiveness of Ra-223 in the post-chemo setting will be evaluated against the active comparators AA and EN. Material and Methods: A Markov model with five health states is used to describe disease progression and evaluate the cost-effectiveness. The health states are: progression-free survival (PFS) without a symptomatic skeletal event (SSE), progressed disease without SSE, PFS after experiencing a SSE, progressed disease after experiencing a SSE, and death. Disease progression is measured by alkaline phosphatase (comparator=BSoC) or prostate specific antigen. Efficacy, safety and quality adjusted life year (QALY) data were extracted from Phase III RCT's. Efficacy and safety of Ra-223 versus AA and EN was obtained by indirect treatment comparisons. The model has been validated by specialists treating mCRPC. Analyses were performed from a societal perspective, including costs outside the health care budget. Results: Compared to BSoC, Ra-223 has higher quality adjusted survival (0.29 QALYs) and lifetime costs (€22.485) in mCRPC patients, resulting in an incremental cost-effectiveness ratio of €78.642 per QALY. This is below the proposed Dutch threshold of €80.000. Probabilistic sensitivity analyses reveal a 33% chance for Ra-223 to be cost-effective compared to BSoC at this threshold. Cost-effectiveness of Ra-223 in the postchemo setting compared to active comparators is as follows. While quality adjusted survival of Ra-223 is similar to AA, Ra-223 has lower lifetime costs (€5.905), which are mainly driven by lower drug and SSE treatment costs. Probabilistic sensitivity analyses show a 78% chance for Ra-223 to be cost-effective compared to AA at a threshold of €80.000. Compared to EN, Ra-223 has a slightly lower QALY gain (-0.06) and lower lifetime costs (-€7.255), resulting in only a 19% chance of EN to be cost-effective compared to Ra-223 at a €80.000 threshold. Conclusions: Our model suggests that Ra-223 may be cost-effective compared to BSoC and AA in the Netherlands, with Ra-223 even dominating AA (evaluated in post-chemo patients only). Although EN may lead to slightly more health in post-chemo patients, this health gain is accompanied by extra costs resulting in EN not being considered costeffective compared to Ra-223 according to the Dutch threshold. Ra-223's cost-effectiveness compared to AA and EN should be interpreted with caution due to indirect treatment comparisons.