Editor’s Note: At the recent "Yangtze Breast Cancer Collaboration Mid-Year Meeting and the Mid-Year Meeting of the Oncology Drug Clinical Research Committee of the Chinese Medical Education Association," Professor Leiping Wang from Fudan University Shanghai Cancer Center delivered a keynote presentation titled “New Advances in HER2-Positive Breast Cancer at ASCO 2025 and My Clinical Practice.” Oncology Frontier invited Prof. Wang for an exclusive interview to share insights on the key findings presented at the ASCO 2025 conference in the field of HER2-positive breast cancer and their clinical implications, along with perspectives on future research directions.Oncology Frontier: In your lecture titled “New Advances in HER2-Positive Breast Cancer at ASCO 2025 and My Clinical Practice,” what were the most important new developments presented at ASCO 2025 in this area?
Prof. Leiping Wang:ASCO 2025 featured several important clinical trial updates. In the field of HER2-positive breast cancer, two Phase III studies stood out and may have a significant impact on clinical practice.
For HER2-positive advanced breast cancer (HER2+ ABC), a key clinical question has been whether trastuzumab deruxtecan (T-DXd/DS-8201a), either alone or combined with pertuzumab (T-DXd + P), could outperform the current first-line standard regimen—THP (taxane + trastuzumab + pertuzumab).
At ASCO 2025, the global, multicenter Phase III DB-09 trial directly challenged the THP standard and produced highly encouraging results. The study exceeded expectations in terms of overall efficacy, hazard ratio, and subgroup analyses. The combination of T-DXd and pertuzumab achieved a median progression-free survival (PFS) of 40.7 months and reduced the risk of disease progression or death by 44% compared to the THP regimen. This represents a major shift—bringing T-DXd from later-line to first-line therapy—and could influence clinical decision-making, particularly where economic conditions permit broader access.
In early-stage HER2-positive breast cancer, the combination of taxanes, carboplatin, trastuzumab, and pertuzumab in neoadjuvant therapy has shown excellent results. However, whether certain traditional chemotherapy agents are indispensable remains an open question. Previous findings from the BCIRG-007 study suggested that a de-escalated TH regimen (docetaxel + trastuzumab) without carboplatin offered comparable PFS and overall survival (OS) to the standard TCH (docetaxel + carboplatin + trastuzumab), with similar safety outcomes. Now, with widespread dual-targeted therapy, exploring chemotherapy de-escalation remains a critical area.
At this year’s ASCO meeting, Prof. Kun Wang from Guangdong Provincial People’s Hospital presented the multicenter, open-label, randomized, non-inferiority Phase III neoCARHP study, which evaluated the feasibility of de-escalation in the neoadjuvant setting. The trial enrolled patients with untreated stage II–III HER2-positive invasive breast cancer aged ≥18. Based on nodal and hormone receptor status, patients were randomized (1:1) to receive six 3-week cycles of physician-selected taxanes (docetaxel, paclitaxel, or nab-paclitaxel) plus trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks) and pertuzumab (840 mg loading dose, then 420 mg every 3 weeks), with or without carboplatin (AUC dosing), forming the TCbHP and THP arms, respectively.
For the primary endpoint, 64.1% of patients in the THP group (245/382; 95% CI: 59.2–68.8) and 65.9% in the TCbHP group (253/384; 95% CI: 61.0–70.5) achieved pathological complete response (pCR). The absolute difference was –1.8% (95% CI: –8.5 to 5.0); odds ratio (OR) 0.93 (95% CI: 0.69–1.25); p=0.0089, confirming non-inferiority of THP to TCbHP. Subgroup analysis showed consistent results across hormone receptor statuses: in the ER–/PR– group, pCR rates were 78.2% (THP) vs. 77.8% (TCbHP); in the ER+/PR+ group, 55.8% vs. 58.8%, respectively. These findings suggest that a de-escalated THP regimen without carboplatin may be a safe and effective neoadjuvant strategy, particularly for patients who are less tolerant of platinum or are expected to respond well to targeted therapy.
Oncology Frontier: Based on the latest advances presented at ASCO 2025 in HER2-positive breast cancer and your own clinical experience, how do you foresee the future of research and treatment in this field? Which areas do you believe deserve particular attention and further investigation?
Prof. Leiping Wang: There are indeed several key areas worth close attention. First, the DB-09 study results presented so far are preliminary. It will be important to see whether progression-free survival (PFS) remains consistent or changes with longer follow-up. Another question is whether the monotherapy arm can deliver outcomes comparable to the combination arm. Given that second-line therapies are also highly effective, we are eager to understand the extent to which first-line treatment influences overall survival (OS).
Beyond awaiting more mature data from DB-09, current research has shifted toward maintenance strategies following first-line T-DXd use. One of the major focuses now is how to adjust treatment based on ctDNA monitoring or treatment response assessment.
In early-stage disease, the field is exploring not only the possibility of omitting carboplatin but also reducing the number of chemotherapy cycles. There’s also growing interest in identifying molecular biomarkers that could help select particularly responsive patients who may be spared chemotherapy altogether.
All of these developments highlight the importance of continuous learning and staying up to date, in order to better serve clinical practice.
Prof. Leiping Wang Department of Medical Oncology, Fudan University Shanghai Cancer Center
