The following article features coverage from the European Society for Medical Oncology (ESMO) Congress 2021. Click here to read more of Cancer Therapy Advisor’s conference coverage.

Second-line or later treatment with trastuzumab deruxtecan (T-DXd) prolonged progression-free survival (PFS), compared with trastuzumab emtansine (T-DM1), in patients with HER2-positive, metastatic breast cancer, according to results of the phase 3 DESTINY-Breast03 trial.

These results were presented at the European Society for Medical Oncology (ESMO) Congress 2021 by Javier Cortés, MD, PhD, of the International Breast Cancer Center in Barcelona, Spain.

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“In my opinion, these data support T-DXd becoming the standard of care for second-line HER2-positive metastatic breast cancer,” Dr Cortés said.

The DESTINY-Breast03 trial ( Identifier: NCT03529110) enrolled patients with unresectable or metastatic, HER2-positive breast cancer previously treated with trastuzumab and taxanes in the advanced setting.

A total of 524 patients were randomly assigned to receive T-DXd (261 patients) or T-DM1 (263 patients). At baseline, the median age was about 54 years in both arms, about half of patients had hormone receptor-positive disease, and roughly 70% had visceral disease.

About 10% of patients in each arm had received no prior treatment for metastatic breast cancer, and roughly half had received 1 prior line of therapy in the metastatic setting. Nearly all patients (99.6% in both arms) had previously received trastuzumab, and around 60% in each arm had received pertuzumab.

The median follow-up was 16.2 months for the T-DXd arm and 15.3 months for the T-DM1 arm. The study’s primary endpoint was PFS, and secondary endpoints included overall survival (OS), objective response rate (ORR), and safety.

The PFS was significantly improved with T-DXd. By blinded independent review, the median PFS was not reached with T-DXd and was 6.8 months with T-DM1 (hazard ratio [HR], 0.28; 95% CI, 0.22-0.37; P =7.8 x 10-22). At 12 months, the PFS rates were 75.8% and 34.1%, respectively.

T-DXd improved PFS across all subgroups, regardless of hormone receptor status, prior pertuzumab therapy, visceral disease, prior lines of therapy, and brain metastases.

The median OS was not yet reached in both arms. The 12-month OS rate was 94.1% with T-DXd and 85.9% with T-DM1 (HR, 0.56; 95% CI, 0.36-0.86; P =.007), which did not meet the prespecified boundary for significance.

This was “likely, in my opinion, due to immature follow-up,” Dr Cortés said.

The ORR was 79.7% with T-DXd and 34.2% with T-DM1 (P <.0001). The complete response rates were 16.1% and 8.7%, respectively.

The rates of treatment-emergent adverse events were similar between the arms, and there were no treatment-related deaths in either arm.

Interstitial lung disease/pneumonitis occurred more frequently in the T-DXd arm than in the T-DM1 arm — 10.5% and 1.9%, respectively. In both arms, these events were primarily grade 1 in nature.

“In this first randomized, phase 3 study in breast cancer, T-DXd demonstrated a highly statistically significant and clinically meaningful improvement in progression-free survival compared with T-DM1 in patients with HER2-positive metastatic breast cancer previously treated with taxanes and trastuzumab,” Dr Cortés concluded.

Disclosures: This research was supported by Daiichi Sankyo, Inc., and AstraZeneca. The study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

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


Cortés J, Kim S, Chung W, et al. Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (Pts) with HER2+ metastatic breast cancer (mBC): Results of the randomized phase III DESTINY-Breast03 study. Presented at: European Society for Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. Abstract LBA1.