NICE has requested further information on the use of pembrolizumab (Keytruda) for untreated metastatic or unresectable recurrent PD‑L1-positive squamous cell head and neck cancer (HNSCC) with a combined positive score (CPS) ≥1.
Draft guidance published this week does not recommend the treatment.
NICE is seeking further clarification and analyses, including the following for pembrolizumab monotherapy and pembrolizumab with platinum chemotherapy and 5‑fluorouracil (5‑FU):
- A full comparison of baseline patient characteristics whether cancer started inside or outside the oral cavity.
- Overall survival (OS) data for the two subgroups.
- OS extrapolation curves.
- An alternative utility value for progressed disease, based on published literature.
- Explore techniques to provide full incremental analyses for the two subgroups incorporating a two-year stopping rule and a five-year duration of treatment effect.
In addition, the manufacturer has been requested to carry out alternative analyses using the company's fractional polynomial network meta-analysis and NICE’s evidence review group's approach of using data from KEYNOTE 048 for the comparison of pembrolizumab with platinum chemotherapy and 5‑FU.
The clinical evidence for pembrolizumab came from the KEYNOTE-048 trial carried out on patients with recurrent or metastatic HNSCC who were randomised to receive pembrolizumab monotherapy (n=301), pembrolizumab with platinum chemotherapy and 5-FU (n=281) or cetuximab with platinum chemotherapy and 5-FU (n=300).
It showed that pembrolizumab extended overall survival compared to cetuximab with platinum chemotherapy and 5-FU for the PD-L1 CPS ≥1 subgroup with recurrent or metastatic HNSCC (HR 0.71; 95% CI 0.57-0.89; P=0.0027 for pembrolizumab monotherapy and 0.62; 95% CI 0.50-0.78; P
The draft guidelines are open for public comment until 5 February 2020.