Significant Benefits of T-DXd in HER2+ mBC After T-DM1

May, 05, 2024 | Breast Cancer


  • The DESTINY-Breast02 phase 3 trial aimed to present updated efficacy and safety findings, including OS, for the reported period.
  • The study concluded that T-DXd provides significant benefits over TPC in HER2+ mBC, with a manageable safety profile.

In the randomized, open-label, phase III trial DB-02 (NCT03523585), individuals previously treated with trastuzumab emtansine (T-DM1) for HER2+ metastatic breast cancer were assigned to receive either Trastuzumab deruxtecan (T-DXd) or treatment of physician’s choice (TPC). At the primary analysis (data cutoff [DCO], Jun 30, 2022), T-DXd demonstrated statistically significant enhancements in progression-free survival (PFS) and overall survival (OS) compared to TPC.

Sung-bae Kim and the team aimed to present updated efficacy and safety outcomes, including OS, as of September 29, 2023.

Patients with HER2+ metastatic breast cancer were randomly assigned in a 2:1 ratio to receive either T-DXd or TPC, which consisted of either trastuzumab plus capecitabine (cap) or lapatinib plus cap. This analysis included OS, PFS, PFS from the time of randomization to progression on the next line of therapy or death (PFS2) as assessed by the investigator, and safety outcomes.

About 608 patients were randomized, with 406 receiving T-DXd and 202 receiving TPC. At the DCO, the median (range) follow-up was 30.2 months (0.8-60.7) for T-DXd and 20.5 months (0.0-60.6) for TPC. In the T-DXd and TPC groups, 86.4% and 100% of patients discontinued treatment, respectively, with the primary reason being progressive disease (47.8% and 73.8%, respectively). Median OS was 35.7 months (95% CI 30.9-40.8) with T-DXd compared to 25.0 months (95% CI 20.4-31.5) with TPC.

The median PFS from the time of randomization to the progression on the PFS2 was 33.0 months with T-DXd and 15.0 months with TPC. A subset of patients in both arms received T-DXd as post-study anticancer treatment (12.9% in the T-DXd arm and 46.6% in the TPC arm).

Treatment-emergent adverse events (TEAEs) associated with discontinuation occurred in 21.5% of patients with T-DXd and 9.7% with TPC. Additionally, there were 46 adjudicated drug-related interstitial lung disease/pneumonitis cases with T-DXd, with 4 occurring since the primary DCO (2 grade 1 and 2 grade 2).

The study concluded that patients with HER2+ metastatic breast cancer previously treated with T-DM1 experienced significant benefits with T-DXd compared to TPC. These benefits were demonstrated by clinically meaningful improvements in OS, PFS, and PFS2.

Additionally, the safety profile of T-DXd remained manageable, with no observed long-term toxicity during extended follow-up.

The trial was sponsored by the Daiichi Sankyo.


Clinical Trial:

Kim SB, André F, Takano T, et al. (2024). “Trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2+ metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1): Updated overall survival (OS) results of the randomized phase III DESTINY-breast (DB-)02 study.” Presented at ESMO-BC 2024 (182MO, ID 39)

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