The National Medical Products Administration (NMPA) approved a new indication on 25 December 2025 for the HER2 ADC (Trastuzumab Deruxtecan, T-DXd, Enhertu, DS-8201) developed by AstraZeneca and Daiichi Sankyo. This is for the treatment of patients with unresectable or metastatic hormone receptor (HR)-positive, HER2 low expression (IHC 1+ or IHC 2+/ISH-) or HER2 ultra-low expression (IHC 0 in the presence of cell membrane staining) adult breast cancer who have previously progressed through one or more endocrine treatments in the metastatic disease stage.

PART 1

Approval Basis (DESTINY-Breast06 Study)

This approval of a new T-DXd indication is primarily based on the positive findings of the DESTINY-Breast06 (DB-06) study [1]. The DB-06 study was a global, randomized, open-label Phase III clinical trial. It aimed to evaluate the efficacy and safety of T-DXd and investigator-selected chemotherapy regimens (TPC) in patients with advanced breast cancer with HR+, HER2 low expression, or HER2 ultra-low expression who had previously received endocrine therapy but had not received chemotherapy. The primary endpoint of the study was progression-free survival (PFS) in the HER2 low-expression population, and the key secondary endpoints were overall survival (OS) in the HER2 low-expression population, PFS, and OS in the intent-to-treat (ITT) population (HER2 low expression and HER2 ultra-low expression).

A total of 866 advanced breast cancer patients with ≥ first-line endocrine therapy and no chemotherapy were enrolled in the DB-06 study. This included 713 patients with HER2 low expression and 153 patients with HER2 ultra-low expression. All patients were randomized 1:1 to the T-DXd group (n = 436) and TPC groups (n = 430, Capecitabine [59.8%], Protein-bound paclitaxel [24.4%], Paclitaxel [15.8%]).

By the time of data analysis (18 March 2024), the study had reached the primary endpoint. Specifically:

1. PFS in the T-DXd group was significantly longer by 5.1 months (13.2 months vs 8.1 months, HR = 0.62) compared with the TPC group in the HR+ HER2 low-expression population (Figure 1).

▲ Fig. 1 DESTINY-Breast 06 Study PFS of Population with Low Expression of HR+ and HER2

2. PFS in the T-DXd group also showed beneficial trends in the HR+ HER2 ultra-low expression population (13.2 months vs 8.3 months, HR = 0.78) (Figure 2).

▲ Fig. 2. Study on PFS of HR+ and HER2 Ultra-Low Expression Population by DESTINY-Breast 06

3. PFS was significantly better in the T-DXd group compared with the TPC group in the ITT population (13.2 months vs 8.1 months, HR = 0.63) (Figure 3). In addition, the objective response rate (ORR) and median response duration (DOR) were also better in the T-DXd group than in the TPC group (ORR: 57.3% vs 31.2%, DOR: 14.3 vs 8.6 months) (Figure 4).

▲ Figure 3. DESTINY-Breast 06 Study ITT Population PFS

▲ Figure 4 DESTINY-Breast 06 Study ITT Population ORR and DOR

4. Currently, the OS data is not mature.

PART 2

Summary of Approved Indications for T-DXd

Up to now, T-DXd has been approved for five indications in China, including breast cancer, lung cancer, and gastric cancer ^[2].

PART 3

Summary

HER2 is an important driver gene of breast cancer and also an important target for targeted therapy. In the past, targeted therapy regimens against HER2 were mainly applied to patients with HER2 positivity. However, the most common form of breast cancer is in patients with HR-positive, HER2-negative subtypes. Although classified as HER2-negative, many of these patients actually exhibit some degree of HER2 expression (HER2 low expression or HER2 ultra-low expression). This means that a significant number of patient groups have long been in the dilemma of "having targets but no corresponding targeted drugs". The approval of new indications of T-DXd this time provides a clear and effective follow-up treatment plan for breast cancer patients after resistance to endocrine therapy. It not only opens up a new path of targeted therapy for traditional "HER2 negative" patients but also expands the beneficiary population of anti-HER2 therapy.

References

[1] England Journal of Medicine,2024,391(22):2110-2122.

[2] T-DXd instructions for injection

Statement: This article is only for sharing, if it involves copyright issues, please contact us as soon as possible, we will correct the first time, thank you!