China has become the first country to approve ENHERTU® (trastuzumab deruxtecan, T-DXd) followed by paclitaxel, trastuzumab, and pertuzumab (THP) for the neoadjuvant treatment of HER2-positive early-stage breast cancer, marking the first global approval of this antibody-drug conjugate in a curative-intent early breast cancer setting.
The approval, granted by China’s National Medical Products Administration (NMPA), is based on results from the phase III DESTINY-Breast11 trial, which showed that ENHERTU followed by THP produced a statistically significant and clinically meaningful improvement in pathologic complete response (pCR) compared with standard neoadjuvant therapy. The indication received conditional approval, meaning continued authorization will depend on confirmation of long-term clinical benefit in ongoing studies.
A New Milestone for HER2-Positive Early Breast Cancer
HER2-positive breast cancer accounts for approximately one in five breast cancer cases and is generally associated with more aggressive disease biology and a poorer prognosis than HER2-negative disease. In China alone, about 357,000 breast cancer cases and nearly 75,000 deaths were reported in 2022, underscoring the importance of more effective early treatment strategies.
For patients with HER2-positive early breast cancer, achieving a pathologic complete response after neoadjuvant therapy is one of the earliest markers associated with improved long-term outcomes. Yet approximately half of patients treated with current neoadjuvant approaches still fail to reach pCR, leaving them at greater risk of recurrence. This is particularly important in high-risk stage II or stage III disease, where optimizing preoperative therapy may meaningfully affect long-term prognosis.
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Who Is Covered by the New Approval?
The new approval in China applies to adult patients with HER2-positive breast cancer defined as IHC 3+ or ISH+, specifically those with:
- Stage II high-risk disease
- Stage III disease
The regimen is approved for neoadjuvant treatment, meaning it is given before surgery.
DESTINY-Breast11: Trial Design
DESTINY-Breast11 was a global, multicenter, randomized, open-label phase III trial evaluating several neoadjuvant strategies in high-risk HER2-positive early-stage breast cancer.
A total of 927 patients were enrolled across Asia, Europe, North America, and South America and randomized 1:1:1 to one of three treatment arms:
- Eight cycles of ENHERTU monotherapy
- Four cycles of ENHERTU followed by four cycles of THP
- Four cycles of dose-dense doxorubicin and cyclophosphamide followed by four cycles of THP (ddAC-THP)
The primary endpoint was pathologic complete response, defined as absence of invasive disease in the breast and lymph nodes. Secondary endpoints included event-free survival, invasive disease-free survival, overall survival, and safety.
Importantly, enrollment to the ENHERTU monotherapy arm closed early after a recommendation from the Independent Data Monitoring Committee.
Key Efficacy Results
The most important comparison for the new approval was ENHERTU followed by THP versus standard ddAC-THP.
The pCR rate was:
- 67.29% with ENHERTU followed by THP
- 56.25% with ddAC-THP
This represented an absolute improvement of 11.17% with ENHERTU followed by THP, with a 95% confidence interval of 3.95 to 18.28 and a P value of 0.003.
The pCR benefit was also seen across prespecified subgroups, including both hormone receptor–positive and hormone receptor–negative disease. In the broader trial results previously reported, pCR rates were notably higher in the hormone receptor–negative subgroup, but improvement was observed in both biologic subtypes.
At the time of analysis, event-free survival was immature, with only 4.5% maturity at the data cutoff. However, an early analysis showed a trend favoring the ENHERTU-THP regimen, with an event-free survival hazard ratio of 0.56 (95% CI, 0.26–1.17) compared with ddAC-THP.
The company also noted that efficacy results were consistent in the China subgroup, which adds relevance to the national approval decision.
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Safety Profile
An important aspect of DESTINY-Breast11 was not only the improved pCR rate, but also the favorable tolerability profile compared with anthracycline-based standard therapy.
According to the press release, the safety profile of ENHERTU followed by THP was consistent with the known safety profiles of the individual drugs, with no new safety concerns identified.
Among patients who received at least one dose of ENHERTU 5.4 mg/kg followed by THP (N=320), the most common grade 3 or 4 adverse reactions were:
- Neutropenia: 13.8%
- Diarrhea: 5.9%
- Increased transaminases: 5.0%
- Leukopenia: 4.4%
- Nausea: 1.9%
- Peripheral neuropathy: 1.9%
- Anemia: 1.6%
Grade 5 adverse reactions occurred in 0.3% of patients, including interstitial lung disease (ILD) in 0.3%.
The most frequent adverse reactions leading to permanent discontinuation were:
- Peripheral neuropathy: 2.2%
- ILD: 1.9%
- Increased transaminases: 1.3%
These data are especially important because ILD remains one of the key safety concerns associated with trastuzumab deruxtecan across tumor types and lines of therapy. In DESTINY-Breast11, the ILD rate appears relatively low, but careful monitoring remains essential if this regimen is adopted widely in curative-intent treatment.
Why This Approval Matters
This decision is important for several reasons.
First, it represents the first approval of ENHERTU globally in early breast cancer, extending the drug beyond its already established role in metastatic HER2-positive and HER2-low disease.
Second, it is the first HER2-directed ADC approved in China in the neoadjuvant setting for HER2-positive early breast cancer.
Third, it introduces a regimen that is the first in more than a decade to show both a clinically meaningful pCR improvement and favorable safety profile over a conventional anthracycline-containing approach in this setting, according to the companies’ statement.
This raises the possibility that T-DXd followed by THP could become a new neoadjuvant standard for high-risk HER2-positive early breast cancer, particularly if ongoing studies confirm long-term survival benefit.
Regulatory Outlook Beyond China
The press release also confirms that an application for ENHERTU followed by a taxane, trastuzumab, and pertuzumab is currently under review in the United States for neoadjuvant treatment of HER2-positive early-stage breast cancer.
That means China may be the first market to authorize the regimen, but broader regulatory adoption could follow if agencies consider the pCR benefit sufficient and if confirmatory long-term data mature favorably.
Because the Chinese approval is conditional, full approval will depend on verification of clinical benefit in confirmatory studies, particularly those assessing survival-related endpoints.
Broader Context: ENHERTU’s Expanding Role
ENHERTU is already approved in numerous countries across a range of HER2-expressing cancers, including:
- Metastatic HER2-positive breast cancer
- HER2-low metastatic breast cancer
- HER2-ultralow HR-positive metastatic breast cancer in some regions
- HER2-mutant NSCLC
- HER2-positive gastric and gastroesophageal junction adenocarcinoma
- Selected HER2-positive solid tumors in certain settings
This new neoadjuvant approval in China further expands the drug’s footprint and reflects the broader shift toward using ADCs earlier in the course of disease, where cure remains possible.
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Conclusion
China’s conditional approval of ENHERTU followed by THP for neoadjuvant treatment of stage II high-risk or stage III HER2-positive breast cancer marks a major step in early breast cancer care. Based on the DESTINY-Breast11 phase III trial, the regimen improved pathologic complete response from 56.25% with ddAC-THP to 67.29%, with an absolute pCR gain of 11.17% and a P value of 0.003.
Although long-term efficacy data remain immature, the combination of stronger pCR activity and a manageable safety profile supports the view that ADC-based strategies may move into the curative-intent setting and potentially reshape neoadjuvant treatment standards for HER2-positive disease.