OBJECTIVES

DESTINY-Breast01 (NCT03248492) is a Phase II single-arm trial evaluating trastuzumab deruxtecan (T-DXd) in adults with human epidermal growth factor receptor 2-positive (HER2+) unresectable/metastatic breast cancer (u/mBC) after ≥2 anti-HER2 therapies. DESTINY-Breast01 overall survival (OS) data are not sufficiently mature for extrapolation (at time of analysis only 35.3% of patients had died; median follow-up 20.5 months). Long‑term OS estimates were required to inform cost-effectiveness analyses of T‑DXd vs. National Institute for Health and Care Excellence (NICE)-recommended non-targeted chemotherapies (eribulin, capecitabine, vinorelbine). The objective was to explore approaches for estimating long‑term OS using immature data.

METHODS

Clinical experts indicated the shape of the survival curve with T-DXd is expected to be more similar to another HER2-targeted therapy, trastuzumab emtansine (T-DM1), than non-HER2-targeted comparators. The TH3RESA trial investigated T-DM1 as third-line therapy for HER2+ u/mBC with longer follow-up than DESTINY-Breast01 (as of June 2020). T-DXd OS was modelled by generating a hazard ratio (HR) vs. digitised T‑DM1 data using a Cox proportional hazards model, based on DESTINY-Breast01 OS data to 20.5 months (beyond which data was deemed uninformative for modelling given the high level of censoring). The HR was applied to the extrapolated OS curve from TH3RESA. A range of parametric curves were explored. Direct extrapolation of T-DXd OS was also considered. Comparator OS was based on direct extrapolation of published data.

RESULTS

Extrapolation methods demonstrated mean OS gains for T-DXd vs. eribulin, capecitabine, and vinorelbine (51.9 months [assuming a HR vs. T-DM1]; 58.7 months [direct extrapolation] vs. 11.3, 17.8 and 17.8 months, respectively).

CONCLUSIONS

Modelled results show T-DXd is associated with significant gains in OS vs. eribulin, capecitabine, and vinorelbine; these modelled outcomes informed a successful submission to NICE. T-DXd was recently granted reimbursement through the Cancer Drugs Fund to address the need for targeted therapies in patients with HER2+ u/mBC after ≥2 anti-HER2 therapies.