OBJECTIVES

Approximately 13–20% of breast cancers (BCs) are human epidermal growth factor receptor 2-positive (HER2+), associated with clinically aggressive disease and poor prognosis. DESTINY-Breast01 (NCT03248492) is a single-arm trial evaluating trastuzumab deruxtecan (T-DXd) in adults with HER2+ unresectable or metastatic BC (u/mBC) who have received ≥2 prior anti-HER2 therapies. The objective was to evaluate the effectiveness of T-DXd vs. UK-recommended non-targeted therapies (eribulin, capecitabine, vinorelbine).

METHODS

Due to the single-arm design of DESTINY-Breast01, comparative effectiveness was assessed using unanchored matching-adjusted indirect comparisons (MAICs). Relevant studies were identified by systematic literature review (eribulin, four; capecitabine, three; vinorelbine, one). The population included patients with u/mBC and mixed, unknown or HER2+ status who had received ≥2 prior chemotherapy regimens. Patient-level data from DESTINY-Breast01 (June 2020 data-cut) were weighted to match baseline characteristics of published, aggregate-level data for each comparator. Overall survival (OS) data from the vinorelbine study was considered clinically implausible by clinical experts; comparison of OS with vinorelbine is not reported.

RESULTS

The MAICs demonstrated that T‑DXd is associated with significantly longer progression-free survival (PFS) vs. all comparators (point estimates for hazard ratios [HRs] from the MAICs ranged from 0.08–0.22 for eribulin, 0.15–0.25 for capecitabine, and 0.17 for the single vinorelbine comparison). T-DXd also demonstrated significantly longer OS compared with eribulin (MAIC HRs: 0.17–0.34) and capecitabine (MAIC HRs: 0.21–0.37). Additionally, T‑DXd showed significant improvement in response.

CONCLUSIONS

T-DXd may extend PFS and OS vs. current UK-recommended therapies, as demonstrated by these MAICs. A key limitation of MAIC analyses relates to availability of data from comparator trials. Additionally, MAICs assume that all prognostic factors and effect modifiers are known and adjusted for. Potential matching covariates are limited to those reported in the comparator trials and those collected in DESTINY-Breast01. Comparisons are the most robust possible, given the available data and acknowledged limitations.