On 18 July 2018, the NICE published Technology appraisal guidance [TA531] and recommended pembrolizumab as an option for untreated PD‑L1-positive metastatic non-small-cell lung cancer (NSCLC) in adults whose tumours express PD‑L1 (with at least a 50% tumour proportion score) and have no epidermal growth factor receptor (EGFR)-positive or anaplastic lymphoma kinase(ALK)-positive mutations, only if pembrolizumab is stopped at 2 years of uninterrupted treatment or earlier in the event of disease progression and the company provides pembrolizumab according to the commercial access agreement.
Clinical trial evidence shows that pembrolizumab increases the length of time patients live by nearly 16 months compared with chemotherapy. Although there is uncertainty about the long-term treatment benefit of pembrolizumab after treatment is stopped, there was sufficient evidence of an important extension-to-life benefit in patients with untreated stage IV metastatic PD‑L1-positive NSCLC compared with standard care.
The most plausible cost-effectiveness estimate for pembrolizumab compared with chemotherapy is within the range NICE normally considers acceptable for an end-of-life treatment. Therefore, it can be recommended as an option for untreated metastatic PD‑L1-positive (with at least a 50% tumour proportion score) NSCLC if treatment is stopped after 2 years.
Pembrolizumab (Keytruda, Merck Sharp & Dohme) has a marketing authorisation for the first-line treatment of metastatic NSCLC in adults whose tumours express PD‑L1 with at least a 50% tumour proportion score with no EGFR- or ALK-positive tumour mutations.
Dosage in the marketing authorization is200 mg every 3 weeks by intravenous infusion.
The summary of product characteristics recommends treatment with pembrolizumab until disease progression or unacceptable toxicity.
Pembrolizumab is available at a cost of 1,315.00 GBP per 50‑mg vial (excluding VAT; British national formulary online, accessed March 2017). The average cost of a course of treatment is 84,002 GBP based on the list price. The company has a commercial arrangement. This makes pembrolizumab available to the NHS with a discount. The size of the discount is commercial in confidence. It is the company's responsibility to let relevant NHS organisations know the details of the discount.
The clinical effectiveness evidence for pembrolizumab came from KEYNOTE‑024 study. The KEYNOTE-024 trial is generalisable to clinical practice in England.
The NHS England clinical lead stated that all lung cancer centres should be able to offer testing for PD‑L1 status. The clinical expert explained that testing involves an immunohistochemical assay and facilities for this are widely available in histopathology laboratories. However, PD‑L1 tests are complex to interpret and the standard time needed for assessment is 20 minutes. The appraisal committee concluded that PD‑L1 testing could be standardised quickly and, with training, implemented as standard clinical practice in the NHS.