Editor's Note: The 47th San Antonio Breast Cancer Symposium (SABCS) was grandly held from December 10–13, 2024, in San Antonio, USA, showcasing significant global advancements in breast cancer research. During the conference, Dr. Xiaojia Wang from the Cancer Hospital of the University of the Chinese Academy of Sciences (Zhejiang Cancer Hospital) presented several important research findings. These included innovative treatment strategies with the new PD-1/VEGF bispecific antibody Ivosidenib and the novel antibody-drug conjugate (ADC) ARX788. Additionally, multiple real-world studies (RWS) provided valuable clinical insights into intensified adjuvant therapy for early-stage HER2-positive breast cancer, systemic therapy for advanced breast cancer, and breast cancer bone metastases. These contributions amplified the voice of China in breast cancer research at SABCS.Oncology Frontier interviewed Dr. Xiaojia Wang at the conference to share key data from these studies.Oncology Frontier: Your team presented multiple research findings at this SABCS. Could you briefly introduce the core content and major discoveries of these studies?
- Dr. Xiaojia Wang:Our team presented two highlight posters at this year’s SABCS:
First, a clinical study co-led by Professor Qu Zhang Ouyang and myself on the first-line treatment of triple-negative breast cancer (TNBC) with the PD-1/VEGF bispecific antibody Ivosidenib combined with chemotherapy.
This study was previously reported at the European Society for Medical Oncology (ESMO) annual meeting, showing an objective response rate (ORR) of 72.4%. In this update, with a median follow-up of 11.8 months, 36 patients were enrolled, and 35 had completed at least one baseline efficacy assessment. The results showed an even more promising trend, with an ORR of 80% and a disease control rate (DCR) of 100%. Notably, 83.3% of patients had a PD-L1 Combined Positive Score (CPS) <10, indicating insensitivity to endocrine therapy, yet they achieved a DCR of 100%. The median progression-free survival (PFS) for the entire cohort was 9.36 months, with mPFS of 9.30 months observed in both the PD-L1 CPS <10 and CPS <1 groups. This suggests that PD-L1 CPS has minimal impact on treatment efficacy, and patients with PD-L1 CPS ≥10 may potentially benefit even more.
Regarding safety, there were almost no occurrences of specific adverse reactions related to proteinuria, hypertension, or immune/anti-angiogenic toxicity, possibly due to the bispecific antibody’s mechanism in mitigating side effects. Common treatment-emergent adverse events (TEAEs) were mainly chemotherapy-related, such as elevated transaminases and hematologic toxicity. Therefore, Ivosidenib combined with chemotherapy shows significant promise as a first-line treatment for TNBC.
Second, the ACE-Breast-08 study on ARX788.This single-arm study evaluated the novel anti-HER2 antibody-drug conjugate (ADC) ARX788, developed by Zhejiang NewMed Biopharma, for later-line treatment of HER2-positive advanced breast cancer. In China, second-line treatments for HER2-positive breast cancer often involve tyrosine kinase inhibitors (TKIs) or ADCs, with TKIs being more accessible due to earlier inclusion in medical insurance. Consequently, most patients in second-line and beyond have received TKI therapy. This study focused on this patient population, with participants having undergone a median of three prior treatment lines (ranging from 1–9).
The results showed a median PFS of 6.90 months based on investigator assessment and 5.68 months per independent review committee (IRC) evaluation. Historically, TKIs have achieved around a 6-month mPFS in second-line settings, and in the DESTINY-Breast03 study, trastuzumab emtansine (T-DM1) had an mPFS of 6.8 months. Thus, ARX788’s mPFS of approximately 5–7 months in patients pre-treated with trastuzumab and TKIs in third-line and beyond is encouraging. Future data releases will be worth following.
Regarding safety, the main adverse events included elevated transaminases and interstitial lung disease (ILD), with one TEAE-related death. However, other patients’ side effects were manageable, supporting ARX788’s overall safety and efficacy.
Additionally, we presented four real-world studies (RWS) as posters at SABCS:
1. A real-world study on bone metastases conducted by my graduate team, providing retrospective analysis of the current status of breast cancer bone metastases, treatment drug applications, and bone-related events in Zhejiang Cancer Hospital. This offers valuable real-world data to guide clinical diagnosis and treatment of advanced breast cancer with bone metastases.
2. A real-world clinical study by my team on the novel anti-HER2 therapy Inotuzumab Ozogamicin for advanced HER2-positive breast cancer, demonstrating favorable mPFS in both first- and second-line treatments. We are further exploring its performance across various treatment lines and prior therapies to optimize its clinical use.
3. The NER-Tree study, co-led by Professor Jin Zhang and me, examined the intensified adjuvant therapy with the TKI Neratinib for early-stage HER2-positive breast cancer. The prior ExteNET study suggested that Neratinib improved outcomes in high-risk patients receiving single-target (neo)adjuvant therapy. Given the current preference for dual-target therapy, the NER-Tree study analyzed real-world use and safety of Neratinib to provide evidence for future applications.
4. A real-world study on Sacituzumab Govitecan (SG), involving 44 patients from five centers. After a median of three prior treatment lines, SG achieved a notable real-world median PFS (rPFS) with good safety and tolerability. This highlights SG as a promising option for patients with TNBC and HR+/HER2- advanced breast cancer.
Oncology Frontier: Based on the current evidence for ARX788, what role do you foresee it playing in the future treatment of advanced breast cancer? Could it potentially become a new standard treatment option for specific patient populations?
- Dr. Xiaojia Wang:As mentioned earlier, in China, patients with advanced HER2-positive breast cancer often receive medications like Pyrotinib, which are already covered by medical insurance, for second-line therapy. In the future, ADCs might also become part of standard treatment strategies. ARX788, as a novel ADC, has completed its Phase III clinical trials and is likely to become a significant clinical treatment option moving forward. The ACE-Breast-08 study enrolled 138 patients and demonstrated reliable progression-free survival (PFS) and response rates among patients who had received an average of three prior treatment lines. These results provide solid supporting data for clinical practice, making ARX788 a treatment worth ongoing attention.
Oncology Frontier: Your research team conducted an in-depth analysis of 737 breast cancer patients with bone metastases and identified significant associations between the timing of bone metastasis onset and several clinical factors. What is the clinical significance of these findings for guiding bone metastasis screening and early treatment in breast cancer patients?
Dr. Xiaojia Wang:Bone metastasis is a very common complication in breast cancer, typically occurring in the later stages of the disease. However, we found that bone metastases can also appear early and are sometimes the first sign of breast cancer metastasis. This real-world study highlights the importance of not overlooking the screening, assessment, and treatment of bone metastases in daily clinical practice. Generally, breast cancer-related bone metastases are relatively manageable. However, if patients also present with metastases to other organs, treatment strategies should be carefully considered. Combining anti-tumor therapies with bone-targeted treatments can potentially offer patients a longer survival benefit.
Reference
[1] Xiaojia Wang, et al. PS3-05: Evaluation of the Safety and Efficacy of Ivonescimab in Combination with Chemotherapy as First-Line (1L) Treatment for Triple-Negative Breast Cancer (TNBC). 2024 SABCS abs#526
[2] Zefei Jiang, Xiaojia Wang, Weimin Xie, et al. 2024 SABCS PS8-05: ACE-Breast-08: a phase I study of ARX788, a novel anti-HER2 antibody-drug conjugate, in patients with TKI pretreated HER2 positive advanced breast cancer. 2024 SABCS abs#1607
[3] Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2023 Jan 14;401(10371):105-117.
[4] XiaoJia Wang, Mengyu Ding, Hai Hu, et al. 2024 SABCS P3-08-14 Analysis of the Occurrence Time of Bone Metastasis and Disease Treatment Patterns in 737 Patients with Breast Cancer Bone Metastasis A Retrospective Study from China. 2024 SABCS abs#1131
[5] Huanhuan Zhou, Chao Deng, Xiaojia Wang, et al. 2024 SABCS P5-05-14 Real World Treatment Patterns and Clinical Outcomes of Inetetamab combined with pyrotinib plus chemotherapy in Her 2 negative metastatic breast cancer patients a multi center retrospective study. 2024 SABCS abs#1733
[6] Jin Zhang, Haiguang Liu, Xiaojia Wang, et al. 2024 SABCS P5-07-19 A multicenter prospective non interventional study to investigate the treatment patterns of neratinib in Human Epidermal Growth Factor Receptor 2 positive HER2 early breast cancer EBC in China NER Tree study An interim analysis on safety. 2024 SABCS abs#1101
[7] Chan A, Moy B, Mansi J, et al. Final Efficacy Results of neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial [published online ahead of print, 2020 Oct 6]. Clin Breast Cancer. 2020;S1526-8209(20)30258-5. doi:10.1016/j.clbc.2020.09.014
[8] Huanhuan Zhou, XiaoJia Wang, Zhanhong Chen, et al. 2024 SABCS P3-07-24: Real-World Treatment Patterns and Clinical Outcomes of Sacituzumab Govitecan in HER2 negative metastatic breast cancer patients in China. 2024 SABCS abs#1722.
Dr. Xiaojia Wang
- Doctor of Medicine, Chief Physician (Level II)
- Doctoral and Postdoctoral Supervisor
- Department of Breast Oncology, Zhejiang Cancer Hospital
- Vice Chairman, Zhejiang Immunology Society
- Deputy Director, Zhejiang Cancer Intelligent Diagnosis and Molecular Technology Research Center
- Deputy Director and Chair of the Breast Cancer Quality Control Expert Committee, Zhejiang Cancer Diagnosis and Treatment Quality Control Center
- Vice Chairman, Breast Cancer Expert Committee, Chinese Society of Clinical Oncology (CSCO)
- Standing Committee Member, Breast Cancer Professional Committee, Chinese Anti-Cancer Association
- Standing Committee Member, Medical Ethics Committee, Chinese Anti-Cancer Association
- Member, Cardio-Oncology Group, Cardiovascular Branch, Chinese Medical Association
- Chairman, Oncology Internal Medicine Branch, Zhejiang Medical Association
- Chairman, Breast Cancer Professional Committee, Zhejiang Anti-Cancer Association
- Former Chairman, Oncology Internal Medicine Committee, Zhejiang Anti-Cancer Association
- Honorary Chairman, Cardio-Oncology Committee, Zhejiang Anti-Cancer Association
- Vice President, Zhejiang Translational Medicine Society
- President, Precision Medicine Branch, Zhejiang Translational Medicine Society
