OBJECTIVES:

Surrogate endpoints are increasingly used as substitutes for overall survival (OS) to expedite the approval of cancer drugs. Whilst the EMA accepts the use of surrogates, there is no guidance for their role in determining HTA outcomes. This study aims to explore the relationship between the use of surrogates and HTA outcomes in non-small cell lung cancer (NSCLC) across Germany, France and the UK.

METHODS:

Products receiving EMA marketing authorization for NSCLC between 2012-2022 were filtered to identify those with published appraisals from G-BA, HAS or NICE. Products were categorized by whether they were approved with mature OS data, or with immature OS data and surrogate endpoints (e.g. progression-free survival). HTA outcomes (recommendation/benefit rating, including by subgroup if relevant) were extracted from HTA websites. HTA outcomes of products with OS data versus surrogates were then compared.

RESULTS:

28 products in 49 NSCLC indications were identified, with 42 appraisals completed by G-BA, 29 by HAS and 37 by NICE. In Germany, 12/16 (75%) with mature OS data received an added benefit in at least one subgroup, versus 7/26 (27%) without. The only products to receive a ‘major added benefit’ had mature OS. In France, ASMR III was the highest rating awarded; 6/11 (55%) with mature OS received an ASMR III, versus 2/18 (11%) without. In the UK, 12/15 (80%) with mature OS received a positive recommendation (including Cancer Drugs Fund [CDF]), versus 21/22 (95%) without.

CONCLUSIONS:

Products launching with immature OS data received less favourable HTA outcomes in France and Germany versus those with mature OS. In the UK, the presence of the CDF and acceptance of modelling may provide more flexibility vis-à-vis data at launch. However, manufacturers must consider that launching without mature OS data may have adverse consequences on HTA outcomes in key markets, which could impact pricing and access.