NICE has approved pembrolizumab, with carboplatin and paclitaxel, for use within the Cancer Drugs Fund as an option for untreated metastatic squamous non-small cell lung cancer (NSCLC) in adults but only if pembrolizumab is stopped at two years of uninterrupted treatment, or earlier if the disease progresses.
The main clinical evidence for pembrolizumab with carboplatin and paclitaxel (pembrolizumab combination therapy) comes from the ongoing randomised controlled KEYNOTE‑407 trial. The trial compares pembrolizumab plus carboplatin and paclitaxel or nab-paclitaxel with placebo plus carboplatin and paclitaxel or nab-paclitaxel (standard chemotherapy) for untreated advanced or metastatic squamous NSCLC with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
An interim analysis of KEYNOTE‑407 showed a statistically significant difference in overall survival (OS) and progression-free survival (PFS) in favour of pembrolizumab combination therapy compared with standard chemotherapy. At the most recent data cut-off (April 2018), median OS was 15.9 months for pembrolizumab combination therapy and 11.3 months for standard chemotherapy (hazard ratio [HR] 0.64; 95% CI 0.49-0.85). Median PFS was 6.4 months for pembrolizumab combination therapy and 4.8 months for standard chemotherapy (HR 0.56; 95% CI 0.45-0.70). However, median overall survival was not reached in KEYNOTE‑407 for the subgroup of patients with a PD‑L1 tumour proportion score of 50% or higher in either arm.
Because the clinical evidence is immature, the cost-effectiveness estimates for pembrolizumab combination therapy are also very uncertain. NICE says it may meet the criteria to be considered a life-extending treatment at the end of life when compared with standard chemotherapy, but there is uncertainty about this.
“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,” NICE has announced.