The United Kingdom’s National Institute for Health and Care Excellence has chosen to not recommend abiraterone acetate with prednisone/prednisolone plus androgen deprivation therapy as a treatment for patients with newly diagnosed, high-risk hormone-sensitive metastatic prostate cancer.
The United Kingdom’s National Institute for Health and Care Excellence (NICE) has chosen not to recommend abiraterone acetate (Zytiga) with prednisone/prednisolone plus androgen deprivation therapy (ADT) as a treatment for patients with newly diagnosed, high-risk hormone-sensitive metastatic prostate cancer.1
The committee agreed that data from clinical trials have indicated that the regimen prolongs the time to progressive disease and how long patients live compared with those who receive ADT alone. Additionally, findings from these trials also demonstrated that the approach increases the time until disease progression compared with docetaxel plus ADT; however, the abiraterone regimen has a similar effect regarding overall survival.
“There are concerns that the trials may overestimate the effectiveness of abiraterone,” the agency wrote in the final appraisal document. “This is because the treatments offered in the trials after the disease progresses do not reflect those offered in the National Health Service (NHS), where more people on standard care have effective treatments after their disease progresses than in the trials.”
While Janssen Pharmaceuticals, Inc., the developer of abiraterone, proposed a commercial arrangement to make the agent available in the NHS at a discounted price, this was not agreed upon with NHS England, the agency noted. Regardless, even incorporating the discounted price into cost-effectiveness estimates, the committee concluded that the cost of abiraterone with prednisone or prednisolone plus ADT versus ADT alone or docetaxel plus ADT is still higher than the range considered to be an acceptable use of NHS resources.
The cost of abiraterone is £2,735 (3,374.83) for a pack of 56,500-mg tablets.
“Commercial decisions continued between the company and NHS England and NHS Improvement to identify an arrangement that would support the use of abiraterone as a cost-effective use of NHS resources, but concluded without an agreed arrangement that could be considered by the committee,” the agency wrote in the document.
The clinical evidence used to evaluate the efficacy of abiraterone in combination came from the pivotal phase 3 LATITUDE and STAMPEDE trials.
In the multicenter, randomized, double-blind phase 3 LATITUDE trial, a total of 1119 patients with newly diagnosed high-risk hormone-sensitive metastatic prostate cancer were randomized 1:1 to receive oral abiraterone acetate at 1000 mg once daily plus oral prednisone at 5 mg once daily and ADT (n = 597) or matching placebos plus ADT (n = 602). The coprimary end point of the trial was progression-free survival (PFS) and overall survival (OS).
Results from the final analysis of the trial showed that at a median follow-up of 51.8 months, the median OS was significantly longer in the abiraterone arm compared with the placebo arm, at 53.3 months versus 36.5 months (HR, 0.66; 95% CI, 0.56-0.78; P <.0001).2 Additionally, the median PFS was 33.0 months in the abiraterone arm versus 14.8 months in the control arm (HR, 0.47; 95% CI, 0.39-0.55).
The multi-arm, nonblinded, adaptive STAMPEDE trial enrolled patients with newly diagnosed hormone-sensitive metastatic, node-positive or high-risk localized disease or prostate cancer previously treated with radical surgery or radiotherapy now relapsing with high-risk features. Randomized arms included abiraterone plus ADT plus 5 mg of prednisolone once daily versus ADT alone, and docetaxel plus ADT plus 10 mg of once-daily prednisolone. The primary end point was OS.
Data were available for 502 patients with metastatic disease in the ADT-alone arm, 500 patients in the abiraterone arm, and 115 in the docetaxel arm. A comparison between abiraterone in combination and ADT alone had been pre-specified in the trial protocol. A post-hoc comparison between abiraterone and docetaxel was completed.
Results showed that abiraterone in combination led to improved PFS versus docetaxel in combination (HR, 0.69; 95% CI, 0.50-0.95).3 However, the HR for OS between the 2 arms was found to be comparable (HR, 1.13; 95% CI, 0.77-1.66), and the point estimated was in favor of the docetaxel arm. Additionally, according to the committee, the HR for PFS in a high-risk metastatic subgroup of the STAMPEDE trial was 0.46 (95% CI, 0.36-0.59); it was 0.54 for OS (95% CI, 0.41-0.70).
“The company considered LATITUDE to be the most relevant trial for appraising the clinical effectiveness of abiraterone in combination,” the agency noted. “It considered STAMPEDE to be less relevant because it included patients with locally advanced and those with metastatic prostate cancer, which was broader than the licensed population for abiraterone.”
The committee reached the conclusion that the abiraterone combination led to an improvement in both PFS and OS versus ADT alone; however, they were uncertain regarding the magnitude of long-term survival gained with the agent in combination due to possible differences in the proportion of patients who had received life-extending treatments post-progression on ADT in both trials compared with clinical practice.
In February 2018, the FDA approved abiraterone acetate tablets for use in combination with prednisone in patients with metastatic high-risk castration-sensitive prostate cancer based on results from the LATITUDE trial. The FDA initially approved the agent in combination with prednisone in 2011 for use in those with metastatic castration-resistant prostate cancer (mCRPC) who had received prior chemotherapy. The indication was expanded in 2012 to include patients with metastatic CRPC.