University of Groningen Abiraterone Acetate for the Treatment of Chemotherapy-Naive Metastatic Castration- Resistant Prostate Cancer Ramaekers,

The National Institute for Health and Care Excellence (NICE) invited Janssen, the company manufacturing abiraterone acetate (AA; tradename Zytiga ), to submit evidence for the clinical and cost effectiveness of AA in combination with prednisone/prednisolone (AAP) compared with watchful waiting (i.e. best supportive care [BSC]) for chemotherapy-naı̈ve patients with metastatic castration-resistant prostate cancer (mCRPC). Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Maastricht University Medical Center, was commissioned as the Evidence Review Group (ERG). This paper presents a summary of the company submission (CS), the ERG report, subsequent addenda, and the development of the NICE guidance for the use of this drug in England and Wales by the Appraisal Committee (AC). The ERG produced a critical review of the clinical and cost effectiveness of AAP based on the CS. An important question in this appraisal was, according to the ERG, whether AAP followed by docetaxel is more effective than BSC followed by docetaxel. In the COU-AA-302 trial, 239 of 546 (43.8 %) AAP patients and 304 of 542 (56.1 %) BSC patients received docetaxel as subsequent therapy, following AA or placebo. The results for this specific group of patients were not presented in the CS; therefore, the ERG asked the company to provide these data in the clarification letter; however, these data were presented as commercial-inconfidence and cannot therefore be reported here. The ERG’s critical assessment of the company’s economic evaluation highlighted a number of concerns, including (a) not using the intention-to-treat (ITT) population; (b) inconsistencies in estimating prediction equations; (c) not fully incorporating the impact of adverse events; (d) incorrectly incorporating the new patient access scheme (PAS); and (e) the assumption that AA non-compliance leads to recoverable drug costs. Although some of these issues were adjusted in the ERG base case, the ERG could not estimate the impact of all of these issues, and thus acknowledges that there are still uncertainties concerning the cost-effectiveness evidence. With the exception of the ERG’s preference for using the ITT population, the AC agreed with the approach taken in the ERG base case. The original company and ERG base-case incremental cost-effectiveness ratios (ICERs) were £46,722 and £57,688 per QALY gained, respectively; these changed to £28,563 and £38,061 per QALY gained, respectively, in the revised base cases applying a new PAS. Regarding the end-of-life criteria, after 24 months approximately 63 % of patients in the control group of the COU-AA-302 trial were still alive, and the median survival was 30.1 months (95 % CI 27.3–34.1). Therefore, it is unlikely that life expectancy would be less than 24 months. The AC stated that the most plausible ICER is likely between £28,600 and £32,800 per & Bram L. T. Ramaekers bram.ramaekers@mumc.nl 1 Department of Clinical Epidemiology and Medical Technology Assessment (KEMTA), Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands 2 Kleijnen Systematic Reviews Ltd, York, UK 3 Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands 4 Department of Pharmacy, University of Groningen, Groningen, The Netherlands 5 Institute of Health Policy and Management, iMTA-Institute for Medical Technology Assessment, Erasmus University Rotterdam, Rotterdam, The Netherlands 6 School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands PharmacoEconomics (2017) 35:191–202 DOI 10.1007/s40273-016-0445-5