Kadcyla (ado-trastuzumab emtansine)

ctDNA-positive status after NAT can be switched to ctDNA-negative status in patients treated with T-DM1. Patients who were ctDNA-positive and treated with T-DM1 had a similar RFS to those who were ctDNA-negative, indicating that "ctDNA positivity" could be a marker determining adjuvant T-DM1 therapy.

Early-stage breast cancer is primarily managed with surgery, combined with chemotherapy, radiotherapy, endocrine therapy, and targeted therapies (such as trastuzumab and pertuzumab), significantly improving cure rates...Agents such as T-DM1 and T-DXd have significantly prolonged progression-free survival and overall survival in HER2-positive patients, providing critical treatment options for advanced-stage patients, markedly improving survival outcomes, and are now being explored in earlier lines of therapy, reshaping the treatment landscape of breast cancer...Based on the latest research advances in ADC therapy for breast cancer and incorporating clinical experience from both domestic and international settings, the Professional Committee on Anticancer Drug Clinical Research of the China Anti-Cancer Association has jointly developed the "Guidelines for managing adverse reactions to antibody-drug conjugates in breast cancer (2025 edition)". This guideline aims to provide healthcare professionals with practical guidance on the early identification, regular assessment, timely management, and follow-up monitoring of ADC-related adverse reactions or events.

Important clinical successes include the results of NOX-A12 drug and data on combined drugs based on trastuzumab in patients with metastatic breast cancer. Furthermore, very high control of breast cancer brain metastases in HER-2 positive cases was demonstrated for trastuzumab-emtansine and trastuzumab-deruxtecan. The last finding indicates the perspective for aptamer targeting glioblastoma tumor cells in conjugation with emtansine or deruxtecan.

Although T-DXd improves clinical outcomes, its adoption as a second-line treatment in Oman poses a substantial financial burden, necessitating careful budget planning to ensure long-term affordability.

Dual HER2 blockade with pertuzumab and trastuzumab demonstrated superior short- and long-term efficacy compared with trastuzumab alone, with each treatment showing a distinct but manageable safety profile.

High-risk clinical features significantly influenced neratinib prescribing. Residual disease did not appear to impact prescribing decisions. These findings suggest biologic risk criteria may serve as practical guidelines for adjuvant neratinib use.

Patients without a pathologic complete response after neoadjuvant chemotherapy plus trastuzumab represent a heterogeneous group. Those with ypT<2, ypN0, and ER-positive residual disease may still achieve excellent iDFS and OS despite absence of adjuvant T-DM1.

HS630 and originator drug Kadcyla® exhibit pharmacokinetic similarity in tumor-bearing mice and cynomolgus monkeys following intravenous infusion. The comprehensive nonclinical evaluations of this study provide robust evidence for regulatory approval, in addition to addressing of key scientific and technical challenges in biosimilar development.

Using HER2 ADCs as a model, the tumor distribution of trastuzumab emtansine and trastuzumab deruxtecan co-administered with the HALA antibody was improved in vivo, translating to equal or greater ADC efficacy across a range of HER2 expression levels. Furthermore, Fc-enhanced HALA antibodies elicited a strong response in an immunocompetent mouse model. These results demonstrate that HALA antibodies can expand treatment ranges beyond high-expression targets and leverage strong immune responses.

Clinical studies of antibody-drug conjugates such as trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan have demonstrated significant improvements in progression-free survival and overall survival across diverse breast cancer patient populations. It covers mechanistic insights, linker-payload innovations, receptor-based targeting approaches, clinical trial progress, and next-generation modalities that extend beyond HER2-directed ADCs. Current challenges, safety profiles, and future opportunities in engineering more selective and effective ADC platforms are also discussed.

The efficacy of T-DXd represents a major advance in HER2-targeted therapy, expanding treatment beyond HER2-positive disease into a wider continuum of HER2 expression. Ongoing clinical development of next-generation ADCs aims to improve efficacy, safety, and access to precision-guided cytotoxic therapy across solid tumors.