Adjuvant Trastuzumab Deruxtecan Versus Trastuzumab Emtansine by Residual Cancer Burden in HER2-Positive Early Breast Cancer: A Decision Analysis
Abstract
BackgroundFor patients with HER2-positive early breast cancer and residual disease after neoadjuvant therapy, escalating adjuvant treatment improves outcomes. In high-risk patients, DESTINY-Breast05 found that trastuzumab deruxtecan (T-DXd) reduced the 3-year risk of recurrence compared with trastuzumab emtansine (T-DM1). T-DXd also carries a risk of fatal interstitial lung disease (ILD). The US FDA approval for adjuvant T-DXd includes all patients with residual disease, including lower-risk patients not represented in the trial. We used decision modeling to project 10-year survival across recurrence-risk groups to aid in clinical decision-making.
MethodsWe modeled outcomes for 50-year-old patients receiving T-DXd or T-DM1 using DESTINY-Breast05 data and published literature. The primary outcome was projected 10-year overall survival (OS); secondary outcomes were breast cancer and ILD deaths per 1,000 patients. Results were stratified by residual cancer burden (RCB) class and estrogen receptor (ER) status.
ResultsAcross 1,000 simulations, mean projected OS differences favored T-DXd in every subgroup, with 10-year gains ranging from 0.3 (95% uncertainty interval [UI], -2.1 to 1.6; RCB-I ER-positive) to 9.7 percentage points (95% UI, 5.7 to 14.1; RCB-III ER-positive). T-DXd yielded higher OS in 71% of RCB-I ER-positive simulations and 94% of RCB-I ER-negative simulations. Per 1,000 patients, T-DXd averted 16 to 113 breast cancer deaths and caused 13 ILD deaths compared with T-DM1, assuming a conservative fatal ILD risk.
ConclusionThese findings favor T-DXd for patients with RCB-II or RCB-III disease. For RCB-I patients, particularly those with ER-positive tumors, the projected survival gain is smaller and sensitive to fatal ILD assumptions.
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BibTeX
@misc{fan2026adjuvant,
title = {{Adjuvant Trastuzumab Deruxtecan Versus Trastuzumab Emtansine by Residual Cancer Burden in HER2-Positive Early Breast Cancer: A Decision Analysis}},
author = {Jane Fan and Axel Stenmark Tullberg and Allison W. Kurian and Jennifer L. Caswell-Jin and James C. Dickerson and Fernando Alarid-Escudero},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.19.26365942},
url = {https://www.medrxiv.org/content/10.64898/2026.10.19.26365942v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Adjuvant Trastuzumab Deruxtecan Versus Trastuzumab Emtansine by Residual Cancer Burden in HER2-Positive Early Breast Cancer: A Decision Analysis
AU - Jane Fan
AU - Axel Stenmark Tullberg
AU - Allison W. Kurian
AU - Jennifer L. Caswell-Jin
AU - James C. Dickerson
AU - Fernando Alarid-Escudero
PY - 2026
DA - 2026/10/19
PB - medRxiv
DO - 10.64898/2026.10.19.26365942
UR - https://www.medrxiv.org/content/10.64898/2026.10.19.26365942v1
AB - BackgroundFor patients with HER2-positive early breast cancer and residual disease after neoadjuvant therapy, escalating adjuvant treatment improves outcomes. In high-risk patients, DESTINY-Breast05 found that trastuzumab deruxtecan (T-DXd) reduced the 3-year risk of recurrence compared with trastuzumab emtansine (T-DM1). T-DXd also carries a risk of fatal interstitial lung disease (ILD). The US FDA approval for adjuvant T-DXd includes all patients with residual disease, including lower-risk patients not represented in the trial. We used decision modeling to project 10-year survival across recurrence-risk groups to aid in clinical decision-making. MethodsWe modeled outcomes for 50-year-old patients receiving T-DXd or T-DM1 using DESTINY-Breast05 data and published literature. The primary outcome was projected 10-year overall survival (OS); secondary outcomes were breast cancer and ILD deaths per 1,000 patients. Results were stratified by residual cancer burden (RCB) class and estrogen receptor (ER) status. ResultsAcross 1,000 simulations, mean projected OS differences favored T-DXd in every subgroup, with 10-year gains ranging from 0.3 (95% uncertainty interval [UI], -2.1 to 1.6; RCB-I ER-positive) to 9.7 percentage points (95% UI, 5.7 to 14.1; RCB-III ER-positive). T-DXd yielded higher OS in 71% of RCB-I ER-positive simulations and 94% of RCB-I ER-negative simulations. Per 1,000 patients, T-DXd averted 16 to 113 breast cancer deaths and caused 13 ILD deaths compared with T-DM1, assuming a conservative fatal ILD risk. ConclusionThese findings favor T-DXd for patients with RCB-II or RCB-III disease. For RCB-I patients, particularly those with ER-positive tumors, the projected survival gain is smaller and sensitive to fatal ILD assumptions.
ER -