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Real-world outcomes of datopotamab deruxtecan after trastuzumab deruxtecan in hormone receptor–positive, HER2-negative metastatic breast cancer
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Real-world outcomes of datopotamab deruxtecan after trastuzumab deruxtecan in hormone receptor–positive, HER2-negative metastatic breast cancer

Breast Cancer·September 2Open Access
Obstetrics & GynecologyLimited evidenceHormone Receptor-Positive HER2-Negative Metastatic Breast CancerRetrospective Cohort StudyAntibody-Drug ConjugateAdultDatrowayEnhertuDatopotamab DeruxtecanTrastuzumab Deruxtecan

Summary

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What was studied

This single-center retrospective study evaluated real-world efficacy of datopotamab deruxtecan (Dato-DXd) in 45 heavily pretreated patients with HR+/HER2− metastatic breast cancer (median 6 prior lines), comparing outcomes in 19 patients with prior T-DXd exposure vs. 26 T-DXd-naïve patients.

Key findings

Overall DCR was 57.8% and ORR 24.4%; in the prior T-DXd group, DCR was 52.6% and ORR 10.5%, with median TTF 3.4 months and median PFS 3.0 months. In T-DXd-naïve patients, DCR was 61.5%, ORR 34.6%, and median PFS 5.1 months. Among 16 patients with evaluable prior T-DXd TTF data, 5 (31.3%) had a longer TTF with Dato-DXd than with prior T-DXd.

Study limitations

- Small single-center cohort (n=45) limits generalizability and statistical power; wide CIs reflect substantial uncertainty. - Prior T-DXd group was more heavily pretreated (2 additional chemotherapy lines), making unadjusted between-group comparisons prone to confounding. - No comparator arm; relative efficacy of Dato-DXd vs. other post-T-DXd options is unknown.

Clinical implications

Dato-DXd can yield disease control in over half of patients previously treated with T-DXd, but response rates and PFS are modest—clinicians should counsel patients on limited but real benefit in this heavily pretreated setting. The ongoing TRADE-DXd trial (NCT06533826) will provide prospective sequencing data.

Caveats

  • Brand name 'Datroway' (FDA-approved name for datopotamab deruxtecan) used; paper uses non-proprietary name only.
  • Sex not explicitly reported as female-only in the paper, but breast cancer context and no mention of male patients strongly implies a female cohort — tagged as female with low uncertainty.
  • Study is from a single Japanese cancer center, which may limit generalizability to other practice settings and ethnic populations.
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  • The T-DXd-naïve group median TTF had an extremely wide 95% CI (0.3–8.3 months), indicating high uncertainty in that subgroup estimate.

Related Questions

Explore related topics

What is the efficacy of datopotamab deruxtecan after trastuzumab deruxtecan in HR+ HER2- metastatic breast cancer?How should ADCs be sequenced in hormone receptor-positive metastatic breast cancer after T-DXd progression?What are the cross-resistance mechanisms between trastuzumab deruxtecan and datopotamab deruxtecan?

Publication Details

Year
2026
Journal
Breast Cancer
Sample Size
n=45
Source
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