1.1 Pembrolizumab, with carboplatin and paclitaxel, is recommended for use within the Cancer Drugs Fund as an option for untreated metastatic squamous non-small-cell lung cancer (NSCLC) in adults only if:
pembrolizumab is stopped at 2 years of uninterrupted treatment, or earlier if disease progresses, and
the company provides pembrolizumab according to the managed access agreement.
1.2 This recommendation is not intended to affect treatment with pembrolizumab, with carboplatin and paclitaxel, 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 metastatic squamous NSCLC is usually platinum-based combination chemotherapy (standard chemotherapy) for people whose tumours express PD‑L1 with a tumour proportion score of lower than 50%, or pembrolizumab monotherapy for people whose tumours express PD‑L1 with a tumour proportion score of 50% or higher.
The main clinical evidence for pembrolizumab with carboplatin and paclitaxel (pembrolizumab combination therapy) comes from an ongoing randomised controlled trial (KEYNOTE‑407). This suggests that people who have pembrolizumab combination therapy live longer than those who have standard chemotherapy. Pembrolizumab combination therapy has only been indirectly compared with pembrolizumab monotherapy in people whose tumours express PD‑L1 with a tumour proportion score of 50% or higher.
Because the clinical evidence is immature, the cost-effectiveness estimates for pembrolizumab combination therapy are very uncertain. It may meet NICE's criteria to be considered a life-extending treatment at the end of life when compared with standard chemotherapy, but there is uncertainty about this. It does not meet the end-of-life criteria when compared with pembrolizumab monotherapy for people whose tumours express PD‑L1 with a tumour proportion score of 50% or higher. Pembrolizumab should be stopped at 2 years of uninterrupted treatment or earlier if disease progresses because the clinical- and cost-effectiveness evidence is limited to 2 years of treatment and the best treatment duration is unknown.
Pembrolizumab combination therapy has the potential to be cost effective, but more evidence is needed to address the clinical uncertainties. Therefore, it is recommended for use in the Cancer Drugs Fund for untreated metastatic squamous NSCLC in adults.