Presentation (CTI)

OBJECTIVES: In certain indolent cancers, patients may undergo periods of active surveillance post-progression prior to receiving treatment. However, as chronic conditions, many patients eventually require multiple lines of treatment. Therefore, there may be value in delaying the time until a new treatment is required. Time-to-next-treatment (TTNT) is a common endpoint in trials of indolent diseases but the extent of its impact on health technology assessment (HTA) outcomes is unclear. This analysis aimed to understand HTA agency views on TTNT and whether TTNT data have positively influenced any HTA outcome.
METHODS: We undertook a targeted review of recent HTA reports (March 2018-March 2025) from four influential agencies - (Canada, [CDA-AMC]; England, [NICE]; France, [HAS] and [G-BA]). Four diseases were included (chronic lymphocytic leukemia [CLL] follicular lymphoma [FL], marginal zone lymphoma [MZL] and Waldenström's macroglobulinemia [WM]).
RESULTS: Fifty-one HTA reports were identified and reviewed. Clinical experts consulted by both NICE and CDA-AMC noted that TTNT is an important and relevant outcome measure. Moreover, a NICE committee noted that TTNT may be a more meaningful outcome than progression-free survival, the typical primary endpoint for indolent lymphomas. However, the impact of TTNT on HTA outcomes was limited due to several reasons. Firstly, interpretation of TTNT was limited when based on single-arm trial data, which are common for later-line treatments. Secondly, strict methodological requirements of HTA agencies meant that TTNT results were often not considered. Thirdly, TTNT was only presented as an exploratory endpoint. Finally, a lack of pre-defined clinically meaningful thresholds for TTNT also limited the interpretability of any results.
CONCLUSIONS: TTNT has the potential to be a trial outcome that can impact some HTA evaluations of indolent disease; however, challenges remain in delivering sufficiently robust data packages that allow agencies to recognize the benefits of new treatments based on TTNT.