OBJECTIVES: In the TROPiCS-02 trial, SG provided statistically significant and clinically meaningful improvement in progression-free survival and overall survival versus chemotherapy in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) (IHC 0, 1+, 2+/ISH-) mBC. Separately, T-DxD also demonstrated clinical benefits in patients with HR+/HER2 low (IHC 1+, 2+/ISH-) mBC in the Destiny Breast-04 (DB04) trial. A feasibility assessment for an ITC was needed to understand whether outcomes could be compared indirectly between SG and T-DxD without biases.

METHODS: A targeted literature review was conducted in September 2022 to find clinical trials with SG and T-DxD in in HR+/HER2- mBC. Potential heterogeneities in trial design, population characteristics, and data availability were assessed to evaluate the feasibility of conducting an ITC comparing the two treatments using either unadjusted or population-adjusted methods.

RESULTS: Patients in TROPiCS-02 were more pretreated compared to patients in DB04 (median number of prior chemotherapies: 3 vs 1) and had more severe disease (ECOG 1: 55% vs 45%; liver metastases: 86% vs 70%). There were differences in comparator arm therapy composition (TROPiCS-02 did not include taxanes vs DB04 did not include vinorelbine) and prior treatment history which preclude unadjusted ITC methods. Data on prognostic factors for the directly overlapping population from both trials was not available, precluding an unbiased adjusted ITC. Population-adjusted ITC using data from single arm trials (IMMU-132-01 and DAISY) were not feasible due to insufficient data on prognostic factors.

CONCLUSIONS: An ITC between these two treatments using data from currently available trials is not feasible due to heterogeneity in study designs, populations and lack of data on prognostic factors in the directly overlapping population. Therefore, no comparative conclusions can be made from an ITC between these two treatments among HR+/HER2- mBC patients.