OBJECTIVES:

The primary goal of this analysis is to identify challenges associated with the HTA evaluation of neo-/adjuvant oncology therapies in major EU countries, given difficulties in demonstrating benefit in payer-preferred outcomes such as overall survival, and outlining factors that can drive favorable HTA outcomes.

METHODS:

Five novel oncology products approved between 2013-2018 in neo-/adjuvant indications were selected for in-depth case studies analyzing HTA outcomes and rationales in the EU3 countries (DEU, FRA, and GBR).

RESULTS:

Some non-traditional or surrogate endpoints such as disease- or relapse-free survival (DFS / RFS) were deemed to be appropriate overall survival (OS) surrogates by HTA bodies when supported by clinician opinions. While the G-BA often rejects surrogate outcomes for OS, DFS / RFS were considered to be patient-relevant in DEU as well, as they indicate avoidance of subsequent therapies. Additional follow-up data was commonly requested by the G-BA and NICE to evaluate long-term survival outcomes, but in some cases the HTA bodies expressed leniency in absence of mature OS.

FRA authorities scrutinized magnitude of benefit for neo-/adjuvant therapies closely, with the perception of limited improvement in the accepted surrogate endpoints resulting in unfavorable rating outcomes. In contrast, the G-BA and NICE were focused on the statistical significance of outcomes, with magnitude of benefit playing a secondary role.

Finally, in some cases the HTA bodies and manufacturers have targeted subpopulations vs. the full label indication, to focus utilization on the subgroups with the largest benefits.

CONCLUSIONS:

In absence of robust evidence supporting benefit in traditional outcomes, surrogate metrics can be leveraged to achieve positive HTA outcomes for neo-/adjuvant therapies in major EU countries. Proactively defining and focusing on the highest risk populations during trial design as well as in further analyses and evidence generation activities can further enhance the opportunity.