Editor’s Note: At the 2025 ESMO Annual Congress, the breast cancer field once again witnessed multiple breakthroughs—ranging from the DESTINY-Breast09 study, which redefined first-line therapy for advanced HER2-positive breast cancer, to DESTINY-Breast05, which provided intensified adjuvant strategies for high-risk early-stage patients, and to ASCENT-03 and TROPION-Breast02, which marked the entry of triple-negative breast cancer (TNBC) into the “first-line ADC era.” Collectively, these advances highlight the increasingly profound impact of antibody–drug conjugates (ADCs) in reshaping breast cancer treatment paradigms.
Particularly noteworthy is the strong presence of Chinese innovation on the international stage. Several domestically developed, first-in-class ADCs—distinguished by novel targets, refined molecular structures, and impressive efficacy data—made their debut, showcasing China’s shift from “follower” to “co-runner,” with emerging potential to lead in select areas.
At the recent 2025 Forum on Innovative Anticancer Drug Clinical Research and the 9th East China Breast Cancer Salon, Oncology Frontier invited Professor Wei Li of Jiangsu Provincial People’s Hospital to summarize key ESMO updates in breast oncology and explore strategies for managing ADC resistance and the future trajectory of China’s innovative therapeutics.
01
Oncology Frontier: You delivered a lecture on “2025 ESMO Breast Cancer Hot Topics and Challenges (HER2+ & TNBC Research Progress).” Which studies from the 2025 ESMO Congress impressed you the most in HER2-positive and triple-negative breast cancer? What were the most groundbreaking findings, and how do you think they will influence clinical practice?
Professor Wei Li:
This year’s ESMO meeting revealed several important clinical trial results. In HER2-positive breast cancer, the most notable updates were the DESTINY-Breast09 results for first-line advanced disease and the DESTINY-Breast05 findings for intensified adjuvant therapy in high-risk early-stage patients.
At the 2025 ASCO meeting, DESTINY-Breast09 reported a historic milestone: in first-line HER2-positive metastatic breast cancer, T-DXd plus pertuzumab achieved a median PFS exceeding 40 months, the longest ever reported. At ESMO, we saw further subgroup analyses demonstrating consistent and clinically meaningful PFS benefits across all subgroups—regardless of prior treatments, hormone receptor status, or PIK3CA mutation status—when compared with THP. These findings could prompt revisions to clinical guidelines for first-line treatment of advanced HER2-positive disease.
For early-stage HER2-positive breast cancer with residual invasive disease after neoadjuvant therapy, DESTINY-Breast05 directly compared T-DXd with T-DM1 in the adjuvant setting. The results showed statistically significant and clinically meaningful improvements in both invasive disease-free survival (IDFS) and disease-free survival (DFS) for T-DXd. This study may drive guideline updates for high-risk early-stage patients.
In the TNBC field, first-line treatment paradigms are being reshaped by TROP2-targeted ADCs. Two phase III trials released at ESMO—ASCENT-03 (evaluating sacituzumab govitecan, SG) and TROPION-Breast02 (evaluating datopotamab deruxtecan, Dato-Dxd)—both achieved success in first-line advanced disease, offering new options beyond conventional chemotherapy.
ASCENT-03 covered mTNBC patients ineligible for immunotherapy. Compared with physician’s-choice chemotherapy, SG significantly improved PFS, reducing the risk of disease progression or death by 38%, extending median PFS to 9.7 months (vs. 6.9 months). Benefits were observed across all prespecified subgroups, and safety remained manageable.
TROPION-Breast02 similarly demonstrated that Dato-Dxd significantly improved both PFS and OS compared with chemotherapy. Median PFS was 10.8 vs. 5.6 months (a 43% reduction in progression/death risk), median OS was 23.7 vs. 18.7 months (a 21% reduction in mortality), and ORR increased to 62.5%, with manageable toxicity (mostly grade 1–2 mucositis and nausea).
Together, these studies indicate that for mTNBC patients who cannot receive PD-(L)1 inhibitors, chemotherapy is no longer the only first-line option. ADCs now offer highly effective targeted treatment alternatives.
02
Oncology Frontier: With the growing availability of ADCs, sequencing and resistance have become major clinical concerns. What strategies do you employ when managing patients who develop resistance or progression on ADCs?
Professor Wei Li:
As the use of ADCs expands, resistance has become increasingly evident, yet standardized post-ADC treatment strategies are still lacking. Current approaches generally include two directions:
- Sequential ADC therapy. Switching to an ADC with a different payload may help overcome resistance, but simply substituting another ADC with the same payload often yields limited benefit.
- Combination strategies to overcome resistance. These include combining ADCs with agents of different mechanisms—such as immune checkpoint inhibitors—to achieve synergistic effects.
However, to fundamentally overcome ADC resistance, we must address the underlying mechanisms of resistance. Precision treatment based on specific resistance pathways will ultimately be the most effective strategy.
03
Oncology Frontier: China has evolved from an early follower to an emerging innovator in the anti-HER2 ADC field. In your view, what is our current level in source innovation and clinical trial design? What breakthroughs are essential for China to move from “co-running” to “leading”?
Professor Wei Li:
In recent years, China’s innovative force in breast oncology has grown rapidly, contributing an increasingly strong “Chinese voice” on the world stage. At ESMO 2025, several domestically developed ADCs—such as SHR-A1811 and A166 targeting HER2, and Sac-TMT targeting TROP2—were prominently featured.
China’s presence is driven by three major innovation engines:
First, differentiated innovation in targets and payloads. We pursue novel targets and high-activity payloads distinct from existing drugs, designing next-generation ADC molecules with enhanced stability, wider therapeutic windows, and stronger bystander effects through advanced linker technologies—achieving true competitive differentiation.
Second, breakthroughs in overcoming clinical resistance. Chinese researchers are addressing resistance mechanisms head-on in ADC design, achieving significant clinical responses in heavily pretreated and refractory populations, thereby extending survival in difficult-to-treat patients.
Third, leadership in multinational clinical research. China now independently conducts and leads MRCTs, combining international standards with Chinese characteristics. We efficiently execute high-quality global trials while focusing on high-incidence or unique patient subgroups in China, generating strong evidence that has earned recognition at major international congresses, including ESMO, with multiple LBA presentations.
These achievements highlight China’s rising influence in advancing global cancer therapy.
About Professor Wei Li
Professor Wei Li Deputy Director, Breast Center Jiangsu Provincial People’s Hospital
