China Approves Neoadjuvant T-DXd Followed by THP for HER2+ Breast Cancer

China’s National Medical Products Administration has granted conditional approval to neoadjuvant trastuzumab deruxtecan (T-DXd; Enhertu) followed by paclitaxel, trastuzumab (Herceptin), and pertuzumab (Perjeta; THP) for the treatment of adult patients with HER2-positive stage II or III breast cancer.¹

This regulatory decision was backed by findings from the phase 3 DESTINY-Breast11 trial (NCT05113251), in which patients with high-risk, HER2-positive early-stage breast cancer who received T-DXd followed by THP (n = 321) achieved a statistically significant and clinically meaningful improvement in pathologic complete response (pCR) rates compared with those who received standard dose-dense doxorubicin and cyclophosphamide (ddAC) followed by THP (ddAC-THP; n = 320).^1,2 Data showed a pCR rate of 67.29% in the T-DXd arm vs 56.25% in the ddAC-THP arm, translating to an 11.17% improvement (95% CI, 3.95%-18.28%; P = .003).¹ Similar pCR rate improvements with the T-DXd–based regimen were seen across most prespecified patient subgroups, including those with hormone receptor–positive and –negative disease.

Notably, the efficacy results from the China subgroup of patients were consistent with those seen in the overall trial population.

“In patients with high-risk, HER2-positive early-stage breast cancer, effective neoadjuvant treatment is critical to lower the risk of disease recurrence, maximize the chance of cure, [and] potentially [enable] less intensive surgery,” Jiong Wu, MD, secretary of the Party Committee of Fudan University Shanghai Cancer Center in China, as well as the China leading primary investigator of the DESTINY-Breast11 trial, stated in a news release. “Findings from DESTINY-Breast11…[suggest] a potential new standard of care in this setting.”

Full approval of this regimen in this indication will depend on the ability of ongoing adjuvant studies to confirm the long-term clinical benefit of the regimen in patients with early or locally advanced breast cancer.

“As the first approval of [T-DXd] globally for the neoadjuvant [management] of HER2-positive early-stage breast cancer and the first HER2-directed antibody-drug conjugate approved in China in this setting, [T-DXd] followed by THP offers patients in China a new treatment option with the opportunity to reach a pCR and the potential for improved long-term outcomes,” Michio Hayashi, the China president of Daiichi Sankyo, added in the news release. “This third approval of [T-DXd] in the [past] 3 months and seventh approval in 3 years reinforces the rapid progress we are making in bringing [T-DXd] to more patients in China, where there is a high incidence of breast cancer and a continued need for new treatment approaches.”

What was the design of DESTINY-Breast11?

This global, multicenter, randomized, open-label trial randomly assigned 927 patients with high-risk, HER2-positive early-stage breast cancer 1:1:1 to receive:

• 8 cycles of T-DXd monotherapy (n = 286)^1,2
• 4 cycles of T-DXd, followed by 4 cycles of THP
• 4 cycles of ddAC, followed by 4 cycles of THP

T-DXd was administered at a dose of 5.4 mg/kg.

The primary end point was pCR. Secondary end points included event-free survival (EFS), invasive disease–free survival, overall survival, and safety.

What additional efficacy and safety findings have been seen in the DESTINY-Breast11 trial?

At the time of the data cutoff, the EFS data were only at 4.5% maturity. However, an early EFS analysis demonstrated a trend favoring the T-DXd arm (HR, 0.56; 95% CI, 0.26-1.17).

The safety profile of T-DXd followed by THP in the DESTINY-Breast11 patient population was consistent with the known safety profiles of each individual therapy, and the investigators reported no new safety signals. The most frequently observed grade 3/4 adverse effects (AEs) among patients who received at least 1 dose of T-DXd at 5.4 mg/kg followed by THP (n = 320) were neutropenia (13.8%), diarrhea (5.9%), increased aminotransaminase levels (5.0%), leukopenia (4.4%), nausea (1.9%), peripheral neuropathy (1.9%), and anemia (1.6%). In total, 0.3% of patients experienced grade 5 AEs, including interstitial lung disease (ILD; 0.3%). The most commonly reported AEs associated with permanent treatment discontinuation were peripheral neuropathy (2.2%), ILD (1.9%), and increased aminotransaminase levels (1.3%).

“[T-DXd] followed by THP is the first treatment regimen in more than a decade to demonstrate a clinically meaningful improvement in pCR and safety in the neoadjuvant setting for patients with HER2-positive early-stage breast cancer, underscoring the significance of this new approval,” Dave Fredrickson, executive vice president of the Oncology Hematology Business Unit at AstraZeneca, concluded in the news release.¹ “[T-DXd] is already an important option in the metastatic setting, and this decision will bring it into early-stage disease where cure is possible.”

What is the regulatory status of neoadjuvant T-DXd followed by THP for HER2-positive breast cancer in the US?

The FDA has accepted for review a supplemental biologics license application (sBLA) seeking the approval of this regimen for the treatment of adult patients with high-risk, HER2-positive, stage II or III breast cancer.³ The sBLA submission was also supported by data from DESTINY-Breast11.

References

1. Enhertu followed by THP approved in China as the first and only HER2 directed ADC for the neoadjuvant treatment of HER2 positive breast cancer. News release. Daiichi-Sankyo. March 27, 2026. Accessed March 27, 2026. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202603/20260327_E.pdf
2. Harbeck N, Modi S, Pusztai L, et al. Neoadjuvant trastuzumab deruxtecan alone or followed by paclitaxel, trastuzumab, and pertuzumab for high-risk HER2-positive early breast cancer (DESTINY-Breast11): a randomised, open-label, multicentre, phase III trial. Ann Oncol. 2026;37(2):166-179. doi:10.1016/j.annonc.2025.10.019
3. Enhertu followed by THP supplemental biologics license application accepted in the U.S. for patients with high-risk HER2 positive early-stage breast cancer prior to surgery. News release. Daiichi-Sankyo. October 1, 2025. Accessed March 27, 2026. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202510/20251001_E.pdf