Fifth Bincheng Multidisciplinary Breast Cancer Conference
Editor’s Note: The Fifth Bincheng Multidisciplinary Breast Cancer Conference, hosted by the First Affiliated Hospital of Dalian Medical University, was recently held with great success. At the event, Professor Hua Yang from the Affiliated Hospital of Hebei University delivered an in-depth presentation on recent advances in the treatment of HER2-positive metastatic breast cancer. Following the conference, Oncology Frontier conducted an exclusive interview with Professor Yang, focusing on the key findings of the DB-09 study, its clinical implications, and the efficacy and safety of the novel antibody-drug conjugate (ADC) T-DXd in patients with HER2-positive metastatic breast cancer, including those with brain metastases.Oncology Frontier: The DB-09 study was one of the highlights at ASCO 2025 and marked a breakthrough in the treatment of HER2-positive metastatic breast cancer. Could you walk us through the key findings and explain their relevance to current clinical practice?
Professor Hua Yang: I’m pleased to share some of the latest developments in treating HER2-positive metastatic breast cancer. The DB-09 study was indeed a major highlight at this year’s ASCO Annual Meeting, and many of us were eager to see whether this so-called “Ninth Symphony of Destiny” would deliver on its promise.
Following the release of the phase Ib/II DB-07 study last year, which showed encouraging data for DS-8201 (T-DXd), both as monotherapy and in combination with pertuzumab (P) in exploratory settings for metastatic breast cancer, expectations for the large-scale phase III DB-09 study were high. In DB-07, the combination of T-DXd and pertuzumab achieved an impressive objective response rate (ORR) of 84.0%, with a 12-month progression-free survival (PFS) rate of 89.4%—clearly very promising.
In the DB-09 trial, eligible patients with HER2-positive metastatic breast cancer were randomized in a 1:1:1 ratio into three treatment arms:
- T-DXd + placebo
- T-DXd + pertuzumab (T-DXd+P)
- Trastuzumab + pertuzumab + docetaxel (THP)
At this conference, data were primarily presented comparing the T-DXd+P arm with the THP arm. The results demonstrated a significant clinical benefit for T-DXd+P, both in progression-free survival assessed by the blinded independent central review (BICR) and by investigators.
According to BICR, the median PFS was 40.7 months in the T-DXd+P group compared to 26.9 months in the THP group, with a hazard ratio (HR) of 0.56 (95% CI: 0.44–0.71; P < 0.00001). This indicates a 44% reduction in the risk of disease progression or death, making T-DXd+P a highly compelling option for first-line treatment of metastatic HER2-positive breast cancer.
Data from the T-DXd monotherapy arm have not yet been released and are expected upon study completion. Nonetheless, the efficacy of T-DXd+P in the first-line setting is now well supported.
Subgroup analyses assessed by BICR showed consistent PFS benefits across all subgroups, including patients with PIK3CA mutations and those who had previously received HER2-targeted therapies in the neoadjuvant setting.
Compared to earlier trials such as CLEOPATRA and PHILA, the patient population in DB-09 better reflects the complexities of real-world clinical practice. As such, the findings offer meaningful guidance for current treatment decisions.
Oncology Frontier: In the DB-09 study, the novel ADC demonstrated remarkable efficacy in HER2-positive metastatic breast cancer. However, safety concerns—particularly interstitial lung disease (ILD)—have drawn attention. What are your views on the long-term use of T-DXd? In clinical practice, how can dosing or combination strategies be optimized to balance efficacy and safety?
Professor Hua Yang: In the DB-09 study, the combination of T-DXd and pertuzumab (T-DXd+P) achieved a median progression-free survival (PFS) of 40.7 months in first-line treatment of HER2-positive metastatic breast cancer. This means that some patients may remain on T-DXd therapy for an extended period. During long-term treatment, adverse events—not just efficacy—become a major factor in determining whether patients can continue therapy.
The most notable adverse event associated with T-DXd is interstitial lung disease (ILD). In the DB-09 trial, ILD of any grade occurred in 12.1% of patients in the T-DXd+P group, compared to only 1.0% in the THP group. However, the incidence of severe ILD (grades 3–5) was low in the T-DXd+P group, with most cases being grade 1 or 2. Overall, the side effects were manageable.
As T-DXd has become more widely used in clinical settings, expert consensus statements and management protocols have been established to help clinicians better recognize and manage T-DXd-related adverse events.
At this year’s ASCO Annual Meeting, one particular study on T-DXd-associated ILD (Abstract No. 1015) attracted broad interest. It explored whether patients who developed grade 1 ILD during treatment could be safely re-challenged with T-DXd. The study reviewed data from more than 1,400 patients across multiple U.S. centers from 2017 to 2024. Among them, 44 patients who experienced grade 1 ILD resumed T-DXd therapy. The findings showed that it was safe to reintroduce the drug in these cases, and that patients continued to derive clinical benefit across diverse real-world populations.
In addition, the study included 19 patients who developed grade 2 ILD and resumed T-DXd treatment. The ILD recurrence rate was similar, suggesting that with proper evaluation and risk assessment, some patients may safely continue therapy even after experiencing pulmonary toxicity.
These findings underscore the importance of individualized management. We must carefully evaluate each patient’s potential benefit from T-DXd, assess the relationship between ILD and underlying comorbidities, and tailor monitoring and treatment strategies accordingly. This approach will help us optimize the long-term use of T-DXd while ensuring patient safety.
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Oncology Frontier: Patients with HER2-positive breast cancer have a high risk of brain metastases. The role of combining local treatments (such as radiotherapy) with systemic therapy remains debated. How do you view the efficacy of novel anti-HER2 ADCs, such as T-DXd, in patients with brain metastases? How should clinicians balance local and systemic approaches in decision-making?
Professor Hua Yang: Brain metastases are common in patients with HER2-positive breast cancer and represent one of the leading causes of mortality in this population. As such, this has been a long-standing clinical challenge and a critical focus of ongoing research. In the early stages, monoclonal antibody therapies had limited efficacy in treating brain metastases due to the blood-brain barrier. However, the emergence of tyrosine kinase inhibitors (TKIs)—notably pyrotinib and tucatinib—marked a major breakthrough and showed encouraging results. Combining systemic therapy with local treatments such as radiotherapy has since become a more effective strategy, gradually improving outcomes for patients with brain involvement.
New-generation antibody–drug conjugates (ADCs), represented by T-DXd, have also demonstrated promising efficacy. Data from pooled analyses of DB-01, DB-02, and DB-03 studies focusing on HER2-positive brain metastases, as well as the results from the DB-12 study presented at last year’s ESMO Congress, all support the role of T-DXd in this setting.
In DB-12, patients previously treated with one or more lines of anti-HER2 therapy were enrolled—263 had baseline brain metastases, and 241 did not. Among those with brain metastases at baseline, the median PFS reached 17.3 months, and the overall objective response rate (ORR) was 71.7%. Notably, T-DXd showed substantial activity in both active and stable brain metastases.
These findings support a growing consensus: for patients with mild or asymptomatic brain metastases who are not in urgent need of local intervention, initiating systemic therapy may be the preferred first-line approach.
At this year’s ASCO Annual Meeting, the Chinese-developed ADC SHR-A1811 also demonstrated promising efficacy in patients with brain metastases. In the REIN study (Abstract No. 1017), led by Professor Min Yan, patients with HER2-positive breast cancer and brain metastases were randomized into three arms:
- Arm 1: SHR-A1811 monotherapy
- Arm 2: SHR-A1811 combined with pyrotinib
- Arm 3: SHR-A1811 combined with bevacizumab
As of December 31, 2024, confirmed intracranial ORR was 84.4% (27/32) in Arm 1 and 72.7% (16/22) in Arm 3. Both groups showed comparable efficacy in terms of intracranial and overall response rates, indicating strong disease control. Median PFS was 13.2 months (95% CI: 10.0–15.4) in Arm 1, while data for Arm 3 were not yet mature.
Considering that most patients enrolled in the study had previously undergone multiple treatments, these results are encouraging for a heavily pretreated population. We look forward to future data releases.
Looking ahead, as more novel therapies enter the field, existing treatment paradigms may shift significantly. However, one constant must remain: for patients with brain metastases, multidisciplinary collaboration is essential. Neither local nor systemic treatment should be overlooked—only by integrating both approaches can we hope to achieve the best possible outcomes for our patients.
Professor Hua Yang
Chief Physician, PhD, Master’s Supervisor
Director, Department of Medical Oncology and Breast Cancer Unit, Affiliated Hospital of Hebei University
