How should we assess the clinical and cost effectiveness of histology independent cancer drugs?

A histology independent cancer drug targets all solid tumours with a certain genomic mutation, regardless of the primary tumour’s histology.1 The US Food and Drug Administration (FDA) has approved three histology independent drugs (pembrolizumab, larotrectinib, and entrectinib) since 2017, and the European Medicines Agency (EMA) approved the first histology independent drug for the European market in 2019 (larotrectinib) (fig 1). Health technology assessment (HTA) bodies, including the National Institute for Health and Care Excellence (NICE), will therefore soon have to assess the value of these drugs to healthcare systems. Histology independent drugs are indicated for a multitude of tumour types, as long as they express the mutation. The prevalence of these mutations is often low, so the clinical evidence to inform reimbursement decisions for histology independent drugs will be immature and based on studies with extremely small sample sizes. This will make it challenging to assess whether the drug will provide value for money to health systems such as the NHS.