New draft guidance from the National Institute for Health and Care Excellence (NICE) suggests apalutamide plus androgen deprivation therapy (ADT) will not be approved as a treatment for hormone-sensitive metastatic disease prostate cancer or hormone-relapsed non-metastatic disease at high risk of metastasising.
Clinical trial evidence suggests that, compared with placebo plus ADT, apalutamide plus ADT increases progression-free survival and overall survival. However, the draft guidance concludes that this evidence is uncertain because in the trials some people could switch from placebo plus ADT to apalutamide plus ADT. Also, some people could have treatments not available in the NHS.
Furthermore, NICE says, some of the assumptions in the economic modelling are also uncertain. The cost-effectiveness estimates are uncertain and higher than what NICE considers an acceptable use of NHS resources. Therefore, apalutamide plus ADT is not recommended for use on the NHS for hormone-relapsed non-metastatic prostate cancer or for hormone-sensitive metastatic prostate cancer.
In the phase 3, randomised, multicentre SPARTAN trial conducted in patients with hormone-relapsed non-metastatic prostate cancer, median metastases-free survival on apalutamide plus ADT was 40.5 months, compared with 15.7 months on placebo plus ADT (hazard ratio [HR] 0.30; 95% CI 0.24-0.36). Median overall survival was 73.9 months and 59.9 months, respectively (HR 0.78; 95% CI 0.64-0.96).
Median time to progression-free survival on first subsequent treatment (PFS2) was 55.6 months and 41.2 months (HR 0.57; 95% CI 0.47-0.68).
Mean change in EQ-5D-3L showed statistically significant improvements in the apalutamide plus ADT arm compared with the placebo plus ADT arm at cycles 21 (mean difference 3.03) and 25 (mean difference 3.28) (P<0.05).
The NICE appraisal committee concluded that apalutamide plus ADT extended metastases-free survival, overall survival, PFS2 and health-related quality of life when compared with placebo plus ADT and was clinically effective.
The phase 3, randomised, multicentre TITAN trial compared apalutamide plus ADT with placebo plus ADT for hormone-sensitive metastatic prostate cancer.
TITAN showed that median radiographic progression-free survival on apalutamide plus ADT was not reached and on placebo plus ADT it was 22.1 months (HR 0.5; 95% CI 0.4-0.6). Data on overall survival and PFS2 are currently confidential. Mean change in EQ-5D-5L visual analogue score showed no statistically significant differences between the treatment arms for all treatment cycles.
The draft guidance is now open for public comment. Comments will be received until Friday, June 11, 2021, and can be submitted here.
This article originally appeared on Univadis, part of the Medscape Professional Network.
