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New HTA Decisions in England
September 2019
Drug name
KEYTRUDA® (pembrolizumab)
Merck Sharp & Dohme
Decision date
Therapeutic area
Therapeutic sub area
Lung cancer
Recommended with restrictions (CDF)
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.
Decision Detail
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.
The ongoing, randomised placebo-controlled trial KEYNOTE‑407 provided the clinical evidence for pembrolizumab with carboplatin and paclitaxel (pembrolizumab combination therapy). This trial compares pembrolizumab plus carboplatin and paclitaxel or nab-paclitaxel with placebo plus carboplatin and paclitaxel or nab-paclitaxel in adults with untreated advanced or metastatic squamous NSCLC with an Eastern Cooperative Oncology Group performance status of 0 or 1. KEYNOTE‑407 did not include the comparator treatment used in NHS clinical practice for the PD‑L1 tumour proportion score of 50% or higher subgroup (that is, pembrolizumab monotherapy). The committee concluded that KEYNOTE‑407 only directly provided evidence relevant to the subgroup of people whose tumours express PD‑L1 with a tumour proportion score of lower than 50%. An interim analysis of KEYNOTE‑407 showed a statistically significant difference in overall and progression-free survival in favour of pembrolizumab combination therapy compared with standard chemotherapy. The committee acknowledged that the KEYNOTE‑407 data were very immature (median follow‑up of 7.8 months) and that this meant there was substantial uncertainty about the size of the benefit. It concluded that treatment with pembrolizumab combination therapy lengthened overall and progression-free survival compared with standard chemotherapy, but that survival benefit was uncertain because the data were very immature. Because the clinical evidence is immature, the cost-effectiveness estimates for pembrolizumab combination therapy are very uncertain, with a highly uncertain most plausible ICER for pembrolizumab combination therapy. Using various assumptions, the ICER (recalculated by the ERG to include the confidential commercial arrangements for pembrolizumab and subsequent treatments) was higher than £50,000 per quality-adjusted life year (QALY) gained. However, the ICER was considered highly 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.