OBJECTIVES : Tumor agnostic indications where the main evidence is generated in single arm basket trial are a challenge in generating evidence for comparative effectiveness using existing methods for HTA such as indirect treatment comparisons. We investigated the role of intrapatient comparisons as a potential solution.

METHODS : Using the retrospectively collected screening data on prior therapies and outcomes for the single arm basket trial STARTRK-2 investigating entrectinib in solid tumors we derived TTNT (Time To Next Treatment) for the subset of patients who were previously treated with systemic therapy and compared to the duration of therapy with the experimental agent using standard Kaplan-Meier survival methods. We also summarised the investigator recorded responses to most recent prior therapy.

RESULTS : The study included 51 efficacy evaluable NTRK Fusion Positive patients of which 31 had received at least one prior systemic therapy (including chemotherapy, immunotherapy and targeted therapy). The median duration of prior therapy was 4.6 months with 95% CI (3.5, 8.0) compared to 14.8 months with 95% CI (10, undefined). Of the 31 patients 16 achieved response (CR/PR) with Entrectinib vs 4 on prior therapy (with 6 missing data).

CONCLUSIONS : For tumor agnostic trials intra-patient comparisons allow to control for differences in patient characteristics and provide evidence of effectiveness compared to standard of care despite limitations in retrospective data collection and that duration of therapy may not correctly capture progression-free survival.