Trodelvy (sacituzumab govitecan-hziy)

The study highlights SG's clinical relevance and the challenge of translating trial efficacy into real-world outcomes, reinforcing the need for further investigation of tolerability in broader populations.

First-generation ADCs, such as Gemtuzumab ozogamicin, demonstrated the proof of concept but suffered from high immunogenicity, poor selectivity, and heterogeneous drug-antibody ratios. Second-generation ADCs introduced stable linkers and humanized antibodies, exemplified by Ado-trastuzumab emtansine (T-DM1), which targets the HER2 receptor in breast cancer...Third-generation ADCs, including Trastuzumab deruxtecan and Sacituzumab govitecan, incorporate site-specific conjugation, higher drug-to-antibody ratios, and potent payloads capable of inducing bystander killing even in tumors with low antigen expression...In conclusion, ADCs exemplify the convergence of molecular biology, immunology, and medicinal chemistry in the pursuit of precision oncology. Their progressive evolution from concept to clinic not only validates Ehrlich's century-old vision but also heralds a new therapeutic era in which cancer treatment achieves unprecedented specificity, efficacy, and improvement in patient outcomes.

Isogenic PDX models of TNBC provide a powerful platform to define molecular mechanisms of acquired carboplatin resistance and uncover actionable therapeutic strategies. Our findings reveal multiple adaptive routes to platinum resistance, including restoration of homologous recombination and activation of alternative DNA repair programs. Synergistic interactions between SG and mTOR inhibition offer a promising avenue for overcoming resistance, supporting further clinical investigation of these combinations in TNBC.

P2, N=80, Active, not recruiting, Gilead Sciences | Trial completion date: Dec 2025 --> Dec 2027

In this selected cohort, CPS status did not correlate with clinicopathological characteristics, but CPS-positive status was associated with inferior survival outcomes. Given the selection and survivor bias inherent to later-line treatment cohorts and the incomplete availability of CPS, these findings should be considered hypothesis-generating.

P2, N=223, Active, not recruiting, Gilead Sciences | Trial completion date: Dec 2025 --> Dec 2026

P2, N=38, Not yet recruiting, The First Affiliated Hospital of Wenzhou Medical UniversitynThe First Affiliated Hospital, Zhejiang University School of Medicine; The First Affiliate | Initiation date: Sep 2025 --> Feb 2026

P=N/A, N=303, Not yet recruiting, Beijing Luhe Medical College Affiliated to Capital Medical University; Beijing Luhe Medical College Affiliated to Capital Medical University

P=N/A, N=31, Not yet recruiting, Fujian Medical University Union Hospital; Fujian Medical University Union Hospital

Antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan and sacituzumab govitecan, demonstrate enhanced central nervous system penetration and tumor-specific cytotoxicity, improving outcomes in both stable and active brain metastases. Emerging therapies like selective estrogen receptor degraders (SERDs) and kinase inhibitors address resistance mechanisms, offering new avenues for personalized treatment. This review underscores the need for survival-prolonging, quality-of-life-preserving strategies with optimized safety profiles, highlighting the evolving landscape of HER2-negative BCBM and LMD management.

This AE exhibits significant cancer species specificity. Early intervention and management of neutropenia are therefore of considerable clinical importance.

SG is a promising therapeutic option, but further studies are needed, especially randomized controlled trials and studies on combinations with immunotherapy, to improve treatment outcomes and quality of life for patients. Importantly, SG also exhibits immunomodulatory potential through the induction of immunogenic cell death and enhancement of immune effector activity, positioning it as a bridge between cytotoxic and immune-based therapeutic strategies in TNBC.