Enhertu (fam-trastuzumab deruxtecan-nxki)

After further progression on chemotherapy, she received trastuzumab deruxtecan (T-DXd), which induced metastatic regression and yielded disease control for approximately 6 months. This case highlights a therapeutic approach for NSCLC with multiple driver alterations and demonstrates the clinical activity of T-DXd in osimertinib-refractory EGFR-mutant disease with a concurrent HER2 alteration.

Recently, positive results from the Destiny Breast 011 (DB11) randomized clinical trial were reported, seemingly supporting T-DXd followed by paclitaxel, trastuzumab, and pertuzumab as a potential new neoadjuvant treatment option for high-risk, HER2-positive early breast cancer (eBC). Taken together, these limitations substantially constrain the interpretability of the trial's findings. In this commentary, we discuss why, although the DB11 results are encouraging and justify continued exploration of this innovative therapeutic strategy, the current evidence remains insufficient to support upfront neoadjuvant T-DXd as a standard-of-care option for patients with high-risk, HER2-positive eBC.

T-DXd induced clinically meaningful ORRs, with safety consistent with the known profile. Data further support T-DXd as a therapeutic option for pretreated HER2-expressing gynecologic cancers.

T-DXd did not demonstrate sufficient activity to expand enrollment to the planned second stage in patients with OST. No new safety signals were observed.

HER2-low tumors are eligible for HER2-targeted antibody-drug conjugates (ADCs), while T-DXd is approved for HR-positive HER2-ultralow metastatic BC after endocrine therapy...HER2-ultralow shows distinct evolution and high HER2-low conversion potential, affecting ADC eligibility. Routine HER2-0 subclassification and metastatic HER2 reassessment appear clinically useful and warrant prospective validation.

P3, N=1635, Active, not recruiting, Daiichi Sankyo | Trial completion date: Dec 2030 --> Jun 2028 | Trial primary completion date: Dec 2025 --> Jul 2025

More importantly, even among specimens unanimously categorized as IHC 0, there were ~15% specimens classified as 1+ by QDB. Our results supports the QDB HER2 assay as an alternative option to guide T-DXd daily usage by distinguish Her2-low from Her2 0 while setting the stage for outcome-based patient stratification.

ADCs targeting Trop-2, HER2, and FRα have demonstrated notable efficacy in clinical trials, such as Sacituzumab Govitecan (SG) and Trastuzumab Deruxtecan (T-DXd), which have shown high objective response rates in Trop-2 and HER2-positive patients, respectively. However, ADCs still face challenges regarding resistance and safety, and future efforts must focus on optimizing designs and exploring more emerging targets to achieve the goals of precision medicine. This article provides a focused narrative overview of recent advances in ADCs for the treatment of endometrial cancer, with a primary focus on key targets including Trop-2, HER2, FRα, and Nectin-4.

Here, we report a case of a patient with metastatic lung adenocarcinoma who developed acquired high-level HER2 amplification (20 copies) after 2nd-line Osimertinib. Plasma next-generation sequencing (NGS) further confirmed successful inhibition of HER2 amplification. .

P2, N=72, Active, not recruiting, AstraZeneca | Trial completion date: Mar 2026 --> Jun 2026

P3, N=506, Active, not recruiting, AstraZeneca | Trial completion date: May 2026 --> May 2027

T-DM1 shows dose-dependent hepatotoxicity, while cytochrome P450 3A4 (CYP3A4) inhibitors may increase hepatic accumulation of trastuzumab deruxtecan (T-DXd). Trastuzumab mainly induces hepatocellular and cholestatic injury, whereas T-DM1 involves both HER2-dependent and independent pathways. Diagnosis relies on causality assessment, and most cases are reversible with liver function monitoring and timely dose adjustment.