OBJECTIVES: Tumour-agnostic (or histology-independent) therapies have the potential to reshape the treatment of solid tumours. However, European Health Technology Assessment (HTA) frameworks have traditionally used indication-specific standard of care as the clinical and economic benchmark to evaluate new therapies against. Consequently, determining the value of tumour-agnostic therapies has been challenging. This study examines the barriers posed by trial designs for tumour-agnostic therapies and potential solutions to overcome the health economic challenges.

METHODS: A systematic literature review was conducted to identify the current approach to the design of trials for tumour-agnostic therapies, followed by qualitative semi-structured interviews (n=10) of payers in the EU5 markets to ratify findings from the secondary research, determine challenges presented in the evaluation of tumour agnostic therapies based on their trial design and identify trends followed to mitigate the evaluation risks.

RESULTS: HTA decisions were analysed in this study to identify key payer objections, with the most common being: 1) choice of appropriate comparator, 2) lack of sub-group analyses to demonstrate responses across different tumour types, 3) immature data due to trial length, leading to increased uncertainty. Qualitative validation of HTA reports confirmed the key concerns identified. A total of 19 clinical trials involving tumour-agnostic therapies were also investigated. A trend of significant increase in the number of subjects enrolled was observed. PFS is now more commonly investigated as a primary endpoint compared to ORR. Other changes include measurement of quality of life data (EORTC-QLQ-LC13, EQ-5D-5L, EORTC QLQ-C30, PedsQL) and incorporation of comparator arms.

CONCLUSIONS: Payers had objections related to the trial designs used in recent tumour-agnostic HTA submissions. By leveraging the learnings from these assessments, manufacturers now appear to follow different approaches to trial design including; increasing of the number and length of clinical trials, increasing of the size of the patient population and including comparator arms.