Health technology assessment of four drugs for patients with metastatic castration resistant prostate cancer

Sæterdal I, Desser A, Pike E, Hamidi V, Harboe I, Odgaard-Jensen J, Klemp M
Record ID 32018001073
English
Authors' objectives: To assess the clinical effectiveness, safety and cost-effectiveness of the new drugs used for patients with metastatic castration resistant prostate cancer relative to each other.
Authors' results and conclusions: RESULTS: Our results for clinical effectiveness are based on eight randomized controlled trials, presented in 16 publications. The trials included a total of 7,314 patients, from more than 20 countries in Europe, North America and Asia, with histologically or cytologically confirmed diagnosis of progressive prostate cancer with soft tissue or bone metastases. Our clinical evaluation based on the direct comparisons shows that for the all patients group (patients that had, or had not received chemotherapy), the four drugs probably increase median overall survival slightly compared with passive treatment. Median overall survival was increased by approximately four months for all treatment groups (HR 0.77 (95 % CI 0.70 to 0.93) for abiraterone, HR 0.70 (95 % CI 0.59 to 0.83) for cabazitaxel, HR 0.68 (0.59 to 0.79) for enzalutamide and HR 0.65 (95 % CI (0.48 to 0.87) for radium-223. We have low to moderate confidence in these estimates. All intervention drugs probably increases the progression free survival period slightly (between one to five months) compared with passive treatment (moderate quality evidence). Hazard ratio was 0.56 (95 % CI 0.44 to 0.70) for abiraterone, 0.75 (95 % CI 0.63 to 0.90) for cabazitaxel, 0.22 (95 % CI 0.16 to 0.30) for enzalutamide and 0.64 (0.54 to 0.77) for radium-223). The drugs probably improves the quality of life slightly (moderate quality evidence), but may cause more serious adverse events. 5 Executive summary (abiraterone, cabazitaxel, radium-223) or there may be little or no difference between the treatment groups (enzalutamide) (low or moderate quality evidence). The follow up time in the studies varied from 12 to 49 months. In the docetaxel-naive model incremental cost-effectiveness ratios, which reflect the minimum willingness-to-pay at which a treatment could potentially be considered cost-effective, were NOK 984,163 for abiraterone and NOK 971,465 for enzalutamide. In the post-docetaxel model the incremental cost-effectiveness ratios were NOK 993,004 for radium-223; NOK 789,128 for abiraterone; NOK 1,210,474 for cabazitaxel; and NOK 809,595 for enzalutamide. At a willingness-to-pay of NOK 500,000, to be considered cost-effective for use among docetaxel-naive patients, the prices of abiraterone and enzalutamide would need to drop by approximately 54% and 55%, respectively. For use among postdocetaxel patients treatments could be considered cost-effective with price declines of 47% for abiraterone, 46% for enzalutamide, 67% for radium-223 and 37% for cabazitaxel. CONCLUSION: We have assessed the clinical effectiveness, safety and cost-effectiveness of abiraterone, cabazitaxel, enzalutamide and radium-223 for patients with metastatic castration resistant prostate cancer relative to each other. Our cost-effectiveness analysis indicates that at today’s maximum pharmacy prices (AUP) none of the medications investigated can be considered cost-effective at what has typically been considered a reasonable willingness-to-pay. For the docetaxel-naive patient group rebates on the AUP prices of approximately 54% for abiraterone and 55% for enzalutamide would be necessary for these medications to be cost-effective at a willingness-to-pay of NOK 500,000 per quality-adjusted life year. For post-docetaxel patients, the required rebates would be 47% for abiraterone, 46% for enzlutamide, 67% for radium-223 and 36% for cabazitaxel.
Authors' methods: We have performed this Health Technology Assessment in accordance with our Handbook. We performed a systematic literature search for randomized controlled trials in October 2015 in relevant bibliographic databases. We contacted relevant pharmaceutical companies to obtain additional information. Full text publications of potentially eligible references were retrieved. Two authors reviewed eligible publications independently to identify publications that fulfilled our pre-specified inclusion criteria. We assessed all included studies for risk of bias. One author extracted data from the included clinical trials using a pre-designed data recording form and another author verified the data. We conducted pairwise meta-analyses for each available endpoint for all possible combinations of interventions and controls with available evidence from included trials. 4 Executive summary We performed network-meta-analyses where appropriate according to population, intervention, control and outcome. We ranked the different treatments in terms of their likelihood of leading to the best results for each endpoint by help of the surface under the cumulative ranking curve (SUCRA). Two authors assessed the quality of the direct evidence, indirect evidence and the combined evidence from the network meta-analyses by using the GRADE methodology. Our cost-effectiveness analysis was based on a probabilistic, discrete-time Markov cohort model with three health states: progression free survival, progressed disease and death. We ran separate models for the post-docetaxel and docetaxel-naive patient groups. The post-docetaxel model included all four medications, while the docetaxel-naive model examined only abiraterone and enzalutamide. We adjusted baseline transition probabilities using hazard ratios from the effect section of this report. Clinical experts provided advice about resource use during the course of treatment that we used in cost estimations for the model. We relied on maximum pharmacy retail prices in the cost-effectiveness analyses because price discounts negotiated by the Drug Procurement Cooperation and the pharmaceutical companies are considered confidential.
Details
Project Status: Completed
Year Published: 2016
English language abstract: An English language summary is available
Publication Type: Full HTA
Country: Norway
Pubmed ID: 29553643
MeSH Terms
  • Prostatic Neoplasms, Castration-Resistant
  • Antineoplastic Agents
  • Costs and Cost Analysis
  • Radium
  • Taxoids
  • Antineoplastic Combined Chemotherapy Protocols
  • Androstenes
  • Androgen Receptor Antagonists
Contact
Organisation Name: Norwegian Institute of Public Health
Contact Address: P.O. Box 222 Skoyen, N-0123, Oslo
This is a bibliographic record of a published health technology assessment from a member of INAHTA or other HTA producer. No evaluation of the quality of this assessment has been made for the HTA database.