Enhertu (fam-trastuzumab deruxtecan-nxki)

P2, N=100, Recruiting, Jeeyun Lee | N=50 --> 100

With this technology, we developed trastuzumab deruxtecan, the first DXd-ADC directed toward HER2. Additionally, Dato-DXd showed TROP2-dependent antitumor activity in multiple human cancer cell line-derived and patient-derived xenograft mouse models. Clinically, the global phase III trial targeting hormone receptor-positive, HER2-negative, unresectable or recurrent breast cancer led to its first approval in Japan in December 2024, followed by the approvals in the US and Europe later.

In contrast, TROP2-directed ADCs demonstrate negligible cardiac signals. Given the elevated fatality rate of serious cardiac events associated with T-DXd observed in real-world data, we propose a risk-stratified cardiac monitoring algorithm incorporating high-sensitivity troponin and global longitudinal strain for patients receiving next-generation ADCs.

Particular attention is given to HER2-directed antibody-drug conjugates, especially trastuzumab deruxtecan (T-DXd), which have emerged as an important recent therapeutic advance and have renewed interest in HER2 as an actionable target in selected patients with HER2-expressing cervical carcinoma. This review further highlights the need for biomarker-driven patient selection, standardized HER2 assessment, and rational integration of HER2-directed strategies into precision treatment for CC.

Although HER2-targeted therapies, such as trastuzumab deruxtecan, have shown promising results in HER2-positive bladder cancer, optimal immunohistochemistry (IHC) scoring criteria for urothelial carcinoma remain unclear...Upper GI and breast scoring criteria yield divergent scores in a significant subset of urothelial carcinomas, potentially affecting eligibility for targeted therapy. Associations with histologic subtype and metastatic site support disease-specific diagnostic and therapeutic strategies.

[18F]FDG PET/CT provides significant prognostic information in HER2-low metastatic breast cancer treated with T-DXd. Baseline SULpeak and early PERCIST response enable meaningful risk stratification. The proposed prognostic model requires prospective validation before clinical implementation.

P2, N=120, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.

P4, N=10, Recruiting, City of Hope Medical Center | Trial completion date: May 2026 --> Apr 2027 | Trial primary completion date: May 2026 --> Apr 2027

These findings indicate that dose rounding of trastuzumab deruxtecan to the nearest full vial, within a 10% deviation range, can significantly reduce drug waste and pharmacy costs without compromising safety. This strategy is both safe and feasible in Chinese patients and provides preliminary evidence for cautious implementation, pending validation in larger studies.

Overall, the available real-world evidence supports the clinical effectiveness of tucatinib-based therapies in HER2+ MBC, including heavily pretreated populations, patients with prior exposure to T-DXd, and those with brain metastases. However, gaps remain in the real-world data regarding the safety profile of tucatinib and its impact on health-related quality of life in routine clinical practice.

Tucatinib-based combinations and trastuzumab deruxtecan have demonstrated substantial intracranial activity in prospective trials, shifting the treatment paradigm by supporting systemic therapy even in the presence of active brain metastases. A major limitation remains the underrepresentation of patients with brain metastases in clinical trials. This review summarizes current evidence on systemic therapies for BCBM across subtypes and highlights the need for CNS-inclusive trials and the development of effective CNS-active treatments.

Chemoimmunotherapy is the reference first-line regimen for biomarker-unselected advanced cholangiocarcinoma. Early comprehensive genomic profiling is essential to enable timely, matched targeted therapy and maximize population-level benefit.