China’s National Medical Products Administration (NMPA) has approved trastuzumab deruxtecan as adjuvant treatment for adults with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane- and trastuzumab-based treatment, according to a latest press release from Daiichi Sankyo.
The indication covers patients whose tumors are HER2-positive, defined as immunohistochemistry (IHC) 3+ or in-situ hybridization (ISH)+. The approval is based on the Phase 3 DESTINY-Breast05 trial, which compared trastuzumab deruxtecan with trastuzumab emtansine (T-DM1) in patients with residual invasive disease following neoadjuvant therapy.
Trastuzumab deruxtecan is a HER2-directed antibody-drug conjugate discovered by Daiichi Sankyo and jointly developed and commercialized with AstraZeneca. This is its second early breast cancer approval in China and its fifth approval in the country in less than a year, bringing the total to nine indications.
Zhimin Shao, Director, Fudan University Cancer Institute and Breast Cancer, China, and lead investigator in China of the DESTINY-Breast05 trial, said:
“For patients with HER2 positive early breast cancer that have residual invasive disease following neoadjuvant therapy, these findings represent an important step toward reducing the risk of recurrence and advancing the goal of cure.”
Dr. Shao noted that the trial outcomes highlight the ability of trastuzumab deruxtecan to advance clinical practice in the adjuvant setting due to a significant improvement in invasive disease-free survival over T-DM1.
DESTINY-Breast05 Results Supporting the Approval
In DESTINY-Breast05, trastuzumab deruxtecan reduced the risk of invasive disease recurrence or death by 53% compared with trastuzumab emtansine. The hazard ratio for invasive disease-free survival (IDFS) was 0.47, with a 95% confidence interval of 0.34-0.66 and p<0.0001.
The three-year IDFS rate was 92.4% with trastuzumab deruxtecan, compared with 83.7% with trastuzumab emtansine. The corresponding 95% confidence intervals were 89.7-94.4 and 80.2-86.7. The trial also demonstrated a statistically significant improvement in disease-free survival (DFS). Trastuzumab deruxtecan reduced the risk of disease recurrence or death by 53%, with a hazard ratio of 0.47 (95% CI: 0.34-0.66; p<0.0001).
At three years, the DFS rate was 92.3% in the trastuzumab deruxtecan group and 83.5% in the trastuzumab emtansine group. The results were presented at the 2025 European Society for Medical Oncology Congress and subsequently published in The New England Journal of Medicine.
Trial Design and Patient Population
DESTINY-Breast05 is a global, multicenter, randomized, open-label Phase 3 trial evaluating the efficacy and safety of trastuzumab deruxtecan at 5.4 mg/kg versus trastuzumab emtansine.
The study enrolled 1,635 patients across Asia, Europe, North America, Oceania and South America. Eligible patients had HER2-positive early breast cancer with residual invasive disease in the breast or axillary lymph nodes after neoadjuvant therapy and a high risk of recurrence.
High recurrence risk was defined as either inoperable cancer before neoadjuvant treatment or pathologically positive axillary lymph nodes after neoadjuvant therapy.
The primary endpoint was investigator-assessed IDFS, defined as the time from randomization to the first invasive local, axillary or distant recurrence, or death from any cause. Investigator-assessed DFS was the key secondary endpoint. Other secondary endpoints included overall survival, distant recurrence-free interval, brain metastases-free interval and safety.
Safety Findings
According to the press release, the safety profile of trastuzumab deruxtecan in DESTINY-Breast05 was consistent with previous clinical trials, with no new safety concerns identified.
The release also provided a pooled safety analysis across multiple tumor types in patients treated with trastuzumab deruxtecan at 5.4 mg/kg. These figures were not presented as DESTINY-Breast05-specific adverse reaction rates.
In that pooled analysis, Grade 3 or 4 adverse reactions included neutropenia (18.7%), anemia (8.2%), fatigue (7.4%), leukopenia (6.6%), thrombocytopenia (5.4%), lymphopenia (5.0%) and nausea (4.5%). Other reported Grade 3 or 4 reactions included increased transaminases, hypokalemia, diarrhea, vomiting, decreased appetite and pneumonia.
Grade 5 adverse reactions occurred in 0.9% of patients, including interstitial lung disease (ILD) in 0.7%. Treatment discontinuation due to an adverse reaction occurred in 10.1%, with ILD the most frequent adverse reaction associated with permanent discontinuation, at 7.6%.
Michio Hayashi, China President at Daiichi Sankyo, commented on the new indication following the earlier neoadjuvant approval in China, said:
“Following the approval in China earlier this year for the neoadjuvant treatment of HER2 positive early breast cancer, this new indication highlights the expanding role of trastuzumab deruxtecan across multiple stages of HER2 positive disease including in the curative-intent setting.”
Hayashi noted that this was the medicine’s fifth approval in less than a year, supporting the company’s goal of bringing additional indications to patients.
Mary Guan, General Manager, China Oncology Business at AstraZeneca, highlighted the adjuvant setting for patients with residual invasive disease after neoadjuvant treatment:
“For patients with early breast cancer who have residual invasive disease after neoadjuvant treatment, the adjuvant setting is a critical opportunity to reduce the risk of recurrence and progression to metastatic disease.”
Guan referred to the DESTINY-Breast05 findings, in which more than 92% of patients receiving trastuzumab deruxtecan were free of invasive disease at three years. She described the approval as a further expansion of its role in early-stage HER2-positive breast cancer.
Neoadjuvant Indication Converted to Regular Approval
The DESTINY-Breast05 results also supported the conversion of an existing conditional neoadjuvant approval in China to regular approval.
That indication covers trastuzumab deruxtecan followed by paclitaxel, trastuzumab and pertuzumab (THP) before surgery for adults with HER2-positive stage 2 high-risk or stage 3 breast cancer.
The neoadjuvant regimen had previously received conditional approval based on the Phase 3 DESTINY-Breast11 trial. DESTINY-Breast05 served as the confirmatory trial for this indication.
HER2-Positive Early Breast Cancer and Residual Disease
The press release reports that approximately one in five breast cancer cases is HER2-positive and approximately one in three patients with HER2-positive early-stage breast cancer is considered at high risk of recurrence.
HER2 is a growth-promoting receptor protein expressed on the surface of tumor cells. In breast cancer, HER2 overexpression may result from amplification of the HER2 gene and is often associated with aggressive disease and a poor prognosis.
For patients in China who do not achieve a pathologic complete response after neoadjuvant treatment, the release identifies trastuzumab emtansine as the current standard of care in the HER2-positive adjuvant setting.
The release also cites approximately 376,000 breast cancer diagnoses and nearly 73,000 breast cancer deaths in China in 2024.
Additional Regulatory Approvals and Submissions
Based on DESTINY-Breast05, trastuzumab deruxtecan is also approved in Brazil, Canada, India and the United States for adjuvant treatment of adults with HER2-positive breast cancer who have residual invasive disease following neoadjuvant trastuzumab, with or without pertuzumab, and taxane-based treatment.
Additional regulatory submissions based on the trial are under review in the European Union, Japan and Switzerland.
Separately, a regulatory submission is underway in China for trastuzumab deruxtecan in patients with unresectable or metastatic HER2-expressing solid tumors, defined as IHC 3+, who have received prior treatment or have no satisfactory alternative treatment options. That submission is based on results from DESTINY-PanTumor02, DESTINY-Lung01, DESTINY-CRC02.
You can also read: FDA Approves Tucatinib as Front-Line Maintenance in HER2-Positive Metastatic Breast Cancer.
