China’s NMPA Approves Adjuvant T-DXd for HER2+ Early Breast Cancer With Residual Invasive Disease

China’s National Medical Products Administration (NMPA) has approved fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for the adjuvant treatment of adult patients with HER2-positive (immunohistochemistry [IHC] 3+ or in situ hybridization [ISH]–positive) early breast cancer and residual invasive disease following neoadjuvant therapy with a taxane and trastuzumab (Herceptin).¹

The NMPA approval is supported by findings from the phase 3 DESTINY-Breast05 trial (NCT04622319), in which T-DXd was compared with ado-trastuzumab emtansine (T-DM1; Kadcyla).^1,2 At the interim analysis presented at the 2025 ESMO Congress, T-DXd (n = 818) reduced the risk of invasive disease recurrence or death by 53% vs T-DM1 (n = 817; HR, 0.47; 95% CI, 0.34-0.66; P < .0001). The 3-year invasive disease–free survival (IDFS) rate was 92.4% (95% CI, 89.7%-94.4%) with T-DXd vs 83.7% (95% CI, 80.2%-86.7%) with T-DM1.²

“[These] findings represent an important step toward reducing the risk of recurrence and advancing the goal of cure,” Zhimin Shao, of Fudan University in Shanghai, China, and the China lead investigator for DESTINY-Breast05, stated in a news release.¹

How was the DESTINY-Breast05 trial designed?

DESTINY-Breast05 is a global, multicenter, open-label trial that randomly assigned patients 1:1 to receive T-DXd at 5.4 mg/kg or T-DM1 at 3.6 mg/kg, each given intravenously every 3 weeks for 14 cycles.² Eligible patients had centrally confirmed HER2-positive disease with residual invasive disease in the breast or axillary nodes after at least 16 weeks of neoadjuvant chemotherapy and HER2-directed therapy. Patients also needed to have high-risk disease at presentation prior to neoadjuvant therapy.

The primary end point was IDFS rate, and disease-free survival (DFS) rate was the key secondary end point; distant recurrence–free interval (DRFI), brain metastasis–free interval (BMFI), overall survival, and safety were additional secondary end points. The data cutoff for the interim analysis was July 2, 2025, at which point 153 IDFS events (74% of the 207 targeted) had accrued.

What additional efficacy findings were reported in DESTINY-Breast05?

Fifty-one IDFS events occurred with T-DXd vs 102 with T-DM1. The IDFS benefit with T-DXd was observed across prespecified patient subgroups, including patients with inoperable disease at presentation (HR, 0.41; 95% CI, 0.27-0.63), those with positive nodes after neoadjuvant therapy (HR, 0.43; 95% CI, 0.29-0.62), and Asian patients (HR, 0.53; 95% CI, 0.30-0.93). Notably, the 95% CIs crossed 1 in the operable-disease subgroup (HR, 0.58; 95% CI, 0.34-1.01) and in patients with negative post-neoadjuvant nodes (HR, 0.73; 95% CI, 0.33-1.59).

The 3-year DFS rate was 92.3% (95% CI, 89.5%-94.3%) with T-DXd vs 83.5% (95% CI, 79.9%-86.4%) with T-DM1 (HR, 0.47; 95% CI, 0.34-0.66; P < .0001). Distant recurrence was the first event in 42 patients receiving T-DXd vs 77 patients receiving T-DM1, including CNS recurrence in 17 patients vs 25 patients, respectively. The 3-year DRFI rates were 93.9% (95% CI, 91.4%-95.7%) vs 86.1% (95% CI, 82.5%-89.1%), respectively (HR, 0.49; 95% CI, 0.34-0.71), and the 3-year BMFI rates were 97.6% (95% CI, 96.2%-98.5%) vs 95.8% (95% CI, 93.6%-97.2%), respectively (HR, 0.64; 95% CI, 0.35-1.17).

What safety findings were observed with T-DXd in DESTINY-Breast05?

Among treated patients (T-DXd arm, n = 806; T-DM1 arm, n = 801), grade 3 or higher treatment-emergent adverse effects (TEAEs) occurred in 50.6% vs 51.9%, and serious TEAEs were reported in 17.4% vs 13.6%. Discontinuation due to TEAEs was more common with T-DXd (17.9% vs 12.9% with T-DM1), as were dose interruptions (49.6% vs 41.1%, respectively). More than 72% of patients in each arm completed all 14 cycles of treatment.

Nausea was the most frequent any-grade TEAE with T-DXd (71.3% vs 29.3% with T-DM1), whereas decreased platelet counts were more common with T-DM1 (49.8% vs 21.2% with T-DXd). Any-grade adjudicated drug-related interstitial lung disease occurred in 9.6% of patients receiving T-DXd, most commonly grade 2 (6.5%), with grade 3 events reported in 0.9% of patients and 2 grade 5 events reported (0.2%).

What is the global regulatory status of T-DXd following neoadjuvant therapy for HER2-positive breast cancer?

In May 2026, the FDA approved T-DXd for adult patients with HER2-positive (IHC 3+ or ISH-positive) breast cancer and residual invasive disease after neoadjuvant HER2-targeted therapy, at a dose of 5.4 mg/kg every 3 weeks for up to 14 cycles.³ This regulatory decision was backed by findings from DESTINY-Breast05.

The adjuvant T-DXd indication is also approved in Brazil, Canada, and India, and is under review in the European Union, Japan, and Switzerland.¹

References

1. Enhertu approved in China as adjuvant treatment for patients with residual disease after neoadjuvant treatment for HER2 positive early breast cancer. News release. Daiichi Sankyo. October 8, 2026. Accessed October 8, 2026. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202610/20261008_E1.pdf
2. Geyer CE, Park YH, Shao ZM, et al. Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with high-risk human epidermal growth factor receptor 2–positive (HER2+) primary breast cancer (BC) with residual invasive disease after neoadjuvant therapy (tx): interim analysis of DESTINY-Breast05. Ann Oncol. 2025;36(suppl 2):S1556-S1557. doi:10.1016/j.annonc.2025.09.021
3. FDA approves two separate indications for fam-trastuzumab deruxtecan-nxki in HER2-positive early-stage breast cancer. FDA. May 15, 2026. Accessed May 15, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-two-separate-indications-fam-trastuzumab-deruxtecan-nxki-her2-positive-early-stage