1.1 Pembrolizumab is recommended for use within the Cancer Drugs Fund as an option for treating locally advanced or metastatic urothelial carcinoma in adults who have had platinum-containing chemotherapy, only if:
pembrolizumab is stopped at 2 years of uninterrupted treatment or earlier in the event of disease progression and
the conditions in the managed access agreement for pembrolizumab are followed.
1.2 This recommendation is not intended to affect treatment with pembrolizumab that was started in the NHS before this guidance was published. People having treatment outside this recommendation may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.
Why the committee made these recommendations
Treatment for previously treated locally advanced or metastatic urothelial carcinoma is docetaxel or paclitaxel. Clinical trial evidence shows that pembrolizumab significantly improves overall survival compared with these drugs.
Pembrolizumab meets NICE's criteria to be considered a life-extending treatment at the end of life. The most plausible cost-effectiveness estimate is uncertain because it is not clear which overall survival extrapolation is most appropriate to use for the economic modelling. Based on the company's commercial offer as part of the managed access agreement proposal, and the preferred assumptions and extrapolations, the cost-effectiveness estimates using either the evidence review group's or company's preferred overall survival extrapolation are between £44,504 and £46,447 per quality-adjusted life year (QALY) gained. This is in line with what NICE normally considers acceptable for end-of-life treatments (less than £50,000 per QALY gained), although other plausible estimates are higher. However, the cost-effectiveness estimates assume that, despite a 2-year stopping rule, the effect of pembrolizumab continues for the duration of the model (a lifetime continued treatment effect) which is implausible. Accounting for this effect increases cost-effectiveness estimates, although it's not certain by how much; some plausible estimates are more than £50,000 per QALY gained.
Pembrolizumab has plausible potential to be cost effective. Further data collection would reduce the uncertainty around overall survival and continued treatment effect. Therefore pembrolizumab can be recommended for use in the Cancer Drugs Fund.
Pembrolizumab appears to be more effective for people with urothelial carcinoma expressing the PD-L1 protein than for people who do not express PD-L1. However, the cost-effectiveness results for this group are not reliable so no recommendations can be made.