Abiraterone Acetate for the Treatment of Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: An Evidence Review Group Perspective of an NICE Single Technology Appraisal

Abstract

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-naïve 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-in-confidence 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 QALY gained, and concluded that AAP at this stage in the treatment pathway did not meet the end-of-life criterion for short life expectancy. Moreover, in March 2016, the AC produced the final guidance, stating that AAP is recommended, within its marketing authorisation, as an option for treating mCRPC.

Fig. 1

Visual representation of the DES model (see Figs. 5.1 and 5.2 from the ERG report [3] for more details). DES discrete event simulation, AAP abiraterone acetate in combination with prednisone/prednisolone, BSC best supportive care, PP placebo plus prednisone/prednisolone, ERG Evidence Review Group, ECOG Eastern Cooperative Oncology Group, PS performance score. ^a Patients could die in all stages of the model, except during AAP, BSC (PP), and post-docetaxel treatment. If patients die, they firstly go through the ‘BSC before death’ phase involving palliative care, until death. This consists of the ‘end-of-life’ phase where patients are near death and will not receive additional active treatments that may impact survival, but instead are managed for their pain or other symptoms. ^b BSC (PP) involves active monitoring without active treatments that impact survival (patients are still receiving treatments that palliate symptoms of disease, e.g. corticosteroids). ^c Patients for whom pre-docetaxel treatment was discontinued or in whom disease was progressed were monitored in a BSC (pre-docetaxel) phase prior to commencing docetaxel treatment. No active treatment that impacted survival was provided during this phase (although patients are still receiving treatments that palliate symptoms of disease). ^d Patients started docetaxel only if ECOG PS score <2 (assumed to correspond to Karnofsky PS score ≥60 %). Otherwise, patients moved to ‘BSC before death’ until death. ^e This phase involves no active treatment that has shown to impact overall survival while patients are still receiving treatments that palliate symptoms of disease. Furthermore, it was assumed that if patients received AAP prior to docetaxel they would not be eligible for AAP retreatment post-docetaxel, whereas BSC patients were allowed to receive AAP post-docetaxel