OBJECTIVES: The FDA recently approved two therapies for the treatment of solid tumours with specific genetic features: pembrolizumab and larotrectinib. These are the first therapies to have launched that are histology-agnostic, and there is an increasing number of similar therapies entering the later stages of development. Existing HTA methodologies are established to review products based on their relative value per indication, not necessarily considering value across a range of tumour sites with different characteristics. Therefore, the objective of this research is to investigate the implications for such therapies launching in the near-term and determine how industry stakeholders can adapt to meet the needs of the evolving paradigm.

METHODS: Secondary research was conducted to assess clinical trial design and HTA reports of existing therapies to identify key issues. Primary research, in the form of 60 minute qualitative interviews, was conducted with three payers and two KOLs from the EU to understand evidence expectations and likely challenges to obtaining access.

RESULTS: HTA evaluations of histology-agnostic therapies are likely to prove problematic as the grouped efficacy data are unlikely to be fit for the purpose of assessing comparative benefit within tissue specific indications, as per current HTA frameworks. Key challenges highlighted by payers include the design of histology-agnostic clinical trials, variation in treatment practices and guidelines across tumour types, and difficulty in assessing additional benefit versus standard of care. Payers also expressed concerns about the potential budget impact if histology-agnostic therapies are used in combination with other high cost therapies that have histology-specific indications.

CONCLUSIONS: Until HTA frameworks evolve to better accommodate histology-agnostic therapies, manufacturers will need to engage early and work together with payers and HTA bodies to ensure they are generating the appropriate clinical evidence and to support the development of effective price agreements that can be successfully implemented.