Enhertu (fam-trastuzumab deruxtecan-nxki)

Accordingly, gemcitabine-cisplatin with nivolumab and platinum-based chemotherapy followed by maintenance avelumab remain validated evidence-based alternatives, particularly for cisplatin-eligible patients or in regions where enfortumab vedotin plus pembrolizumab is not readily accessible...Enfortumab vedotin monotherapy retains activity post-platinum and immune checkpoint inhibition, erdafitinib provides a targeted benefit in fibroblast growth factor receptor 3-altered tumors, and trastuzumab deruxtecan has emerged as a later-line option for HER2-positive disease. In parallel, circulating tumor DNA is an emerging biomarker with potential to individualize sequencing strategies, although its clinical application remains investigational. This review synthesizes current evidence and highlights practical considerations, emphasizing the need to balance therapeutic innovation with cost effectiveness, equitable access, and global applicability, while identifying critical research priorities in the post-enfortumab vedotin plus pembrolizumab era.

In HER2 mutant NSCLC patients, loss of HER2 is not a universal mechanism of T-DXd resistance. Collectively, these data highlight multiple mechanisms of resistance to T-DXd that do not result in loss of HER2 TKI responsiveness.

Moreover, BB-1701, a novel HER2-ADC containing eribulin as a payload, to which N87 AR cells are sensitive, exhibited antitumor effects in N87 AR cells in vitro and in vivo. These findings indicate that ABC transporter-mediated drug efflux is an important mechanism underlying T-DXd resistance in HER2-positive gastric and lung cancer models. Furthermore, our study suggests that both targeting drug efflux pathways and utilizing alternative payloads may be effective strategies for overcoming T-DXd resistance in HER2-positive gastric and lung cancers.

After surgery, adjuvant chemotherapy with trastuzumab and pertuzumab was administered...After surgery, chemotherapy with trastuzumab deruxtecan was administered. Eight months later, the lung metastases have disappeared, and the patient is currently under observation. We report a case of pancreatic metastasis following breast cancer surgery.

At the time of tracheotomy, biopsy evaluation revealed that the metastatic left supraclavicular lymph nodes were ER- and HER2-positive; therefore, the treatment was switched to a trastuzumab, pertuzumab, and docetaxel(TPD)combination for HER2-positive recurrent breast cancer. However, PET-CT revealed increased accumulation in the recurrent lesions, and the treatment was switched to trastuzumab deruxtecan (T-DXd). The accumulation of recurrent foci became less pronounced and the patient continued to progress without further deterioration.

P=N/A, N=105, Recruiting, AstraZeneca | N=384 --> 105

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.

Her positive response, which surpassed the median progression-free survival rates seen in clinical trials, highlights the potential of precision medicine, where treatment is customized based on genetic and molecular tumor profiles. These new therapeutic options for difficult-to-treat cancer subtypes expand treatment possibilities, ushering in a new era of personalized and precision-driven oncology.

P2, N=116, Not yet recruiting, Yonsei University

Baseline serum HER2 ECD may be a potential non-invasive predictor of T-DXd response in HER2-positive AGC, particularly in IHC 2+/ISH+ cases. Dynamic HER2 ECD level changes during therapy may also reflect treatment response.

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.

P2, N=35, Not yet recruiting, Xijing Hospital