The following article features coverage from the 2021 San Antonio Breast Cancer Symposium. Click here to read more of Cancer Therapy Advisor’s conference coverage.

The significant improvement in progression-free survival seen in the DESTINY-Breast03 trial with the HER2-targeting antibody-drug conjugate trastuzumab deruxtecan (T-DXd) compared with trastuzumab emtansine (T-DM1) was consistent across subgroups of women with HER2-positive (HER2+) metastatic breast cancer, including those with brain metastases.

“These data support T-DXd becoming the standard of care for second-line HER2+ metastatic breast cancer,” according to Sara A. Hurvitz, MD, of the David Geffen School of Medicine, University of California, Los Angeles, who presented results of the subgroup analysis of the trial at the 2021 San Antonio Breast Cancer Symposium (SABCS).

In the previously presented primary analysis of the trial, T-DXd demonstrated clinically meaningful and statistically significant improvement in progression-free survival compared with T-DM1.

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In the study ( Identifier: NCT03529110), 524 patients were randomly assigned to receive 5.4 mg/kg T-DXd or 3.6 mg/kg T-DM1 every 3 weeks. Patients with clinically stable previously treated brain metastases were eligible as long as there was at least 2 weeks between the end of radiotherapy and enrollment. The primary endpoint was progression-free survival by independent central review.

The median progression-free survival for T-DXd was not reached compared with 6.8 months for T-DM1 (hazard ratio [HR], 0.28; 95% CI, 0.22-0.37).

At the meeting, Dr Hurvitz presented details of the subgroup analysis. She noted that there was consistent progression-free survival and overall response rate benefit observed across subgroups regardless of hormone receptor status, prior pertuzumab, number of prior lines of therapy, visceral disease, and brain metastases at baseline.

“Over 67% of patients by each subgroup benefited or had objective response with T-DXd with most of them exceeding three-quarters of patients having an objective response,” Dr Hurvitz said.

Among patients with brain metastases at baseline, the median progression-free survival with T-DXd was 15 months compared with 3 months for T-DM1 (HR, 0.25; 95% CI, 0.13-0.45). Among patients without brain metastases at baseline, the median progression-free survival was not reached for T-DXd and was 7.1 months for T-DM1 (HR, 0.30; 95% CI, 0.22-0.40). 

Confirmed overall response rate was twice as high for T-DXd compared with T-DM1 (79.7% vs 34.2%). Among patients with brain metastases at baseline, the overall response rate was three times as high with T-DXd (67.4% vs 20.5%).

T-DXd treatment was associated with substantial intracranial response and reduction in central nervous system disease. The intracranial objective response rate for T-DXd was 63.9% compared with 33.4% for T-DM1.

Complete response in the brain was seen for 27.8% for T-DXd compared with 2.8% for T-DM1. Progressive disease was seen in 2.8% of patients assigned to T-DXd compared with 22.2% of patients assigned to T-DM1.

Dr Hurvitz said that overall the safety profiles of T-DXd was manageable and comparable with its known safety profile. Although rates of any treatment-emergent adverse events (TEAEs) and TEAEs of grade 3 or worse were generally similar between arms, exposure-adjusted incident rate were lower with T-DXd compared with T-DM1. Discontinuation because of TEAEs was higher with T-DXd but Dr Hurvitz said the rates were similar for exposure adjusted incidence.

Disclosures: This research was sponsored and designed by Daiichi Sankyo with collaboration from AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Read more of Cancer Therapy Advisor’s coverage of SABCS 2021 by visiting the conference page.


Hurvitz S, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan (T-DXd; DS-8201a) vs. trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): subgroup analyses from the randomized phase 3 study DESTINY-Breast03. Presented at SABCS 2021; December 7-10, 2021; San Antonio, TX. Abstract GS3-01.