In July 2018 the European Medicines Agency restricted the use of pembrolizumab for untreated urothelial carcinoma. It should now only be used in adults with high levels of PD-L1. For more information, see the summary of product characteristics for pembrolizumab.
1.1 Pembrolizumab is recommended for use within the Cancer Drugs Fund as an option for untreated locally advanced or metastatic urothelial carcinoma in adults when cisplatin-containing chemotherapy is unsuitable, only if:
their tumours express PD-L1 with a combined positive score of 10 or more
pembrolizumab is stopped at 2 years of uninterrupted treatment or earlier if the disease progresses and
the conditions of 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
Current treatment for untreated locally advanced or metastatic urothelial carcinoma when cisplatin-containing chemotherapy is unsuitable is carboplatin plus gemcitabine. Atezolizumab is also an option, but only within the Cancer Drugs Fund, because of uncertainty about its clinical effectiveness.
Pembrolizumab has been studied in a single-arm clinical trial (KEYNOTE‑052). It appears to be effective but it's difficult to establish the size of the clinical benefit because it has not been directly compared with other treatments in a clinical trial. Also, the long-term benefits of pembrolizumab are uncertain because the trial is ongoing. These issues mean that the estimates of cost effectiveness are also very uncertain.
Pembrolizumab meets NICE's criteria to be considered a life-extending end-of-life treatment. It has the potential to be cost effective, but more evidence is needed to address the clinical uncertainties. Longer follow‑up data from KEYNOTE‑052 and collecting further data from people taking part in KEYNOTE‑361, which directly compares pembrolizumab with other treatments, would help to address some of the uncertainties. Pembrolizumab can therefore be recommended for use within the Cancer Drugs Fund while further data are collected.