Kadcyla (ado-trastuzumab emtansine) / Roche, AbbVie - LARVOL DELTA

EMILIA and DESTINY: Real-World Sequencing Insights in a HER2-positive Metastatic Breast Cancer with Rare Pancreatic metastasis (ESMO Asia 2025) - "In an attempt to render her no evidence of disease (NED), MDT pursued mastectomy (ypTis) and chest wall radiotherapy, followed by maintenance trastuzumab pertuzumab 1 year...Gemcitabine bridging was administered during visceral crisis, after which trastuzumab emtansine (TDM-1) was commenced, achieving stable disease with marginal regression sustained over six cycles...Repeated biopsy was critical to exclude a second primary and reaffirm HER2 status, enabling optimal therapeutic choice. These observations support further investigation into post–T-DXd sequencing strategies and may inform management of biologically similar patient subgroups in ongoing and future trials."

Clinical • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Pancreatic Cancer • Solid Tumor • ER • HER-2 • PGR

HER2 and TROP2 antibody–drug conjugates in metastatic breast cancer: A systematic review of clinical outcomes (ESMO Asia 2025) - "Background: Antibody-drug conjugates (ADCs) targeting HER2 (trastuzumab emtansine [T-DM1], trastuzumab deruxtecan [T-DXd]) and TROP2 (sacituzumab govitecan [SG]) offer novel treatment opportunities for patients with metastatic breast cancer (mBC). HER2- and TROP2-targeting ADCs demonstrate meaningful survival benefits across different metastatic breast cancer subtypes with manageable toxicity profiles. T-DXd shows improved efficacy over T-DM1 in HER2-positive mBC patients, while SG demonstrates clinical benefit in triple-negative and HR+/HER2-negative populations."

Clinical • Clinical data • Metastases • Review • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Study of the profile of HER2-positive metastatic breast cancer patients receiving T-DM1 biosimilar, in a real-world setting (ESMO Asia 2025) - "This multicentric real-world analysis demonstrates that T-DM1 biosimilar provides comparable efficacy and safety in HER2-positive mBC. Clinical benefit tends to be better when T-DM1 is used early in the treatment lines."

Clinical • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Efficacy and safety of trastuzumab deruxtecan (T-DXd) in HER2-positive (HER2+) advanced breast cancer (ABC) with CNS progression after local treatment: Real-world data (ESMO Asia 2025) - "Median lines of previous treatment in ABC was four (1-8), 47 (84%) pts have received pertuzumab, T-DM1 – 45 (80%) pts, lapatinib – 22 (39%) pts; all 3 anti-HER2 Rx received 15 (27%)pts. T-DXd is effective even in pts with CNS progression previously treated with radiation therapy. No new safety signals were recorded."

Clinical • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Real-world evaluation of a trastuzumab emtansine biosimilar in metastatic HER2-positive breast cancer: A single-centre retrospective analysis from India (ESMO Asia 2025) - "All patients had prior trastuzumab exposure; many were heavily pretreated (taxanes 84.3%, anthracyclines 62.7%, pertuzumab 19.6%, lapatinib 39.2%). This analysis supports the trastuzumab emtansine biosimilar as an effective, well-tolerated option for metastatic HER2-positive breast cancer, demonstrating a meaningful ORR and manageable toxicity profile, with PFS broadly consistent across subgroups. Confirmation in larger studies is warranted."

HEOR • Metastases • Real-world • Real-world evidence • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Utilization of neoadjuvant therapy for stage II-III HER2-positive breast cancer in Vietnam: A 10-year analysis on 2390 patients (ESMO Asia 2025) - "The rate of NAT utilization was significantly higher after pertuzumab and T-DM1 approval for early breast cancer (eBC), as well as after the increase in national health insurance coverage for trastuzumab from 50% to 60% in Vietnam: 19.2% vs. 34.7%, 28.8% vs. 53.2%, and 19.4% vs. 35.8% respectively, p values <0.001. Although NAT has been increasingly implemented, a significant proportion of patients were still treated with upfront surgery. There should be policies to increase patients' affordability to anti-HER2 therapies, and to improve multidisciplinary collaboration between breast surgeons and medical oncologists to ensure access to standard neoadjuvant therapy in Vietnam."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

MODULE 4: Selection and Sequencing of Therapy for Relapsed/Refractory HER2-Positive mBC in the Absence of CNS Involvement (SABCS 2025) - "Sponsored by AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, and Puma Biotechnology Inc. Clinical, biological and practical factors influencing the selection and sequencing of therapy for patients with R/R HER2-positive mBC in the absence of CNS metastases Outcomes documented among patients with previously treated HER2-positive mBC without CNS involvement in pivotal clinical research studies of T-DXd and tucatinib-based combinations Long-term findings with and optimal integration of other evidence-based treatment options, such as neratinib/capecitabine, margetuximab/chemotherapy and T-DM1, into the care of patients with progressive HER2-positive mBC Other promising agents and strategies under investigation for advanced HER2-positive breast cancer Frequency of HER2 mutations in patients with mBC; published findings with neratinib-based therapy for this population"

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Solid Tumor • HER-2

Clinical Outcomes of Trastuzumab Emtansine (T-DM1) Following Trastuzumab Deruxtecan (T-DXd) in Metastatic Breast Cancer: A Single-Center Experience (SABCS 2025) - "Clinical Outcomes of Trastuzumab Emtansine (T-DM1) Following Trastuzumab Deruxtecan (T-DXd) inMetastatic Breast Cancer: A Single-Center ExperienceBackground: HER2-positive metastatic breast cancer (MBC) remains an oncological challenge afterdisease progression to pertuzumab-trastuzumab, and fam-trastuzumab deruxtecan. This study provides real-world evidence of the limited clinical efficacy of T-DM1 following resistant to T-DXd in HER2-positive MBC. Further research is warranted to develop novel therapeutic agents in this subgroup of patients and also to develop strategies to avoid resistant to T-DXd."

Clinical • Clinical data • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Risk Signals of Antibody-Drug Conjugates in Bladder Cancer: A Real-World FAERS Study. (PubMed, Clin Epidemiol) - "Disproportionality analyses, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN), were used to detect significant adverse drug event (ADE) signals for four ADCs in bladder cancer treatment: enfortumab vedotin (EV), sacituzumab govitecan (SG), trastuzumab deruxtecan (DS-8201), and trastuzumab emtansine (T-DM1). This study delineates the safety profiles of ADC therapies for bladder cancer, confirming known risks and identifying potential new signals. The findings highlight the need for ADC-specific monitoring strategies and proactive management protocols to mitigate toxicities, thereby providing essential evidence for clinical decision-making."

Journal • Real-world evidence • Bladder Cancer • Candidiasis • Dermatology • Genito-urinary Cancer • Metabolic Disorders • Oncology • Solid Tumor

Utilization and safety of concurrent antibody drug conjugates alongside extracranial radiation therapy in the real-world setting (SABCS 2025) - "This study aims to assess real-world data on the safety of combining ADCs with extracranial RT.Method A retrospective chart review of patients who received concurrent ADC therapy (trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG), and trastuzumab deruxtecan (T-DXd)) and extracranial RT at a single academic institution was conducted. Importantly, no radiation courses were discontinued due to adverse effects.Conclusion In our study of concurrent use of ADCs with RT to breast and/or chest wall +/- RNI, no unexpected toxicities occurred. This study adds to real-world evidence that extracranial radiation therapy can be safely administered alongside ADCs."

Clinical • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • HER-2

Development and Validation of TROP2/HER2-low/Ki67/HR multiplex-immunofluorescence panel with membrane identification: enabling improved Antibody Drug Conjugate therapy selection (SABCS 2025) - "Currently, two ADC drugs targeting HER2: Trastuzumab emtansine (T-DM1) and fam-trastuzumab deruxtecan-nxki (T-DXd), and two targeting Trop2: Sacituzumab govitecan (SG) and datopotomab deruxtecan-dlnk (Dato-DXd) have gained approval by the FDA in treating metastatic BC, with additional ADCs in development. Results also suggested that the custom membrane cocktail can enhance the subcellular evaluation of biomarkers. The study will be supplemented by an independent patient verification cohort to support forthcoming clinical-utility studies."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • HER-2 • TACSTD2

Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T‑DM1) in patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC): Final analysis from DESTINY-Breast03 (SABCS 2025) - P3 | "Conclusions The final analysis of DESTINY-Breast03 confirms the superior efficacy of T-DXd over T-DM1 in pts with HER2+ mBC whose disease had progressed following prior treatment with trastuzumab and a taxane. The safety profile of T-DXd remains manageable, with no new safety signals observed with longer follow-up."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

A case report of veno-occlusive disease (VOD) in a patient with metastatic triple-negative breast cancer receiving trastuzumab deruxtecan. (SABCS 2025) - "We present a rare case of VOD that occurred in a patient with breast cancer receiving T-DXd.Case Presentation: A 45-year-old female with triple-negative breast cancer developed a rapid metastatic recurrence following neoadjuvant chemo-immunotherapy, then rapid progression while on first-line sacituzumab govitecan...The two most implicated ADCs are gemtuzumab ozogamicin and inotuzumab ozogamicin, utilized in hematologic malignancies. Management of VOD includes defibrotide, a thrombolytic agent that stabilizes the endothelium. On review of the literature, there are reports of VOD occurring after treatment with trastuzumab emtansine, another ADC used in breast cancer... We present a rare case of VOD after receipt of T-DXd in a heavily pretreated patient with metastatic breast cancer."

Case report • Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Cardiac Monitoring in Patients Receiving HER2-Directed Therapy: A Meta-Analysis and Cost-Effectiveness Analysis (SABCS 2025) - "We conducted a meta-analysis to quantify the risk of cardiotoxicity associated with HER2-directed agents and developed a cost-effectiveness model to evaluate alternative frequency of cardiac monitoring in patients with a standard cardiovascular risk profile. We performed a systematic literature search (Ovid MEDLINE, Embase, Cochrane) and included 55 studies (n=39,335) evaluating trastuzumab, pertuzumab, trastuzumab deruxtecan (T-DXd), and trastuzumab emtansine (T-DM1). HER2-directed therapies are associated with low rates of symptomatic cardiotoxicity, particularly T-DM1 and T-DXd. Cost-effectiveness modeling demonstrated diminishing returns with more frequent LVEF monitoring. Future analyses will assess the cost-effectiveness of LVEF monitoring strategies in patients with early-stage or metastatic disease treated with trastuzumab, T-DM1, or T-DXd."

Cost effectiveness • HEOR • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer

Molecular characterization of resistance to antibody drug conjugates in metastatic breast cancer: a prospective analysis from the AURORA US Network (SABCS 2025) - "As ADC1, 42 pts received HER2 ADC (35 trastuzumab deruxtecan, T-DXd; 7 trastuzumab emtansine), 29 TROP2 ADC (28 sacituzumab govitecan, SG; 1 datopotamab deruxtecan) and 1 NECTIN4 ADC. Multiplatform molecular characterization of mBC treated with ADC revealed potential mechanisms of resistance related to downregulation of target expression, payload (e.g., microtubule formation, DNA damage repair) and lysosomal processing. Additional analyses integrating these multimodal data are ongoing. Strategies to overcome resistance, e.g. modifying ADC target, are being evaluated in clinical trials."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • BRCA2 • HER-2 • MED12 • NECTIN4 • TACSTD2

Intracranial Activity and Systemic Efficacy of Trastuzumab Deruxtecan in Breast Cancer Patients with Brain Metastases (SABCS 2025) - "T-DXd demonstrates robust intracranial activity and 12-month survival in breast cancer patients with brain metastases. The pooled IC-CBR of 81% notably exceeds historical benchmarks reported with T-DM1 or chemotherapy, which typically range from 30-50% in this population. Prospective studies are needed to refine patient selection and optimize therapeutic sequencing."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Interplay Between MicroRNAs and Breast Cancer Therapies: Personalized Therapeutic Potential for HER2-Low Breast Cancer. (PubMed, Cancers (Basel)) - "However, recent research has led to the development of antibody-drug conjugates (ADCs), such as trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), with the latter showing promising results in treating these patients. In this context, the interplay between miRNAs and HER2-targeted therapies, particularly their modulation of common essential genes and signaling pathways, could reshape HER2-low therapy strategies to transform current practices aimed at improving the overall patient outcomes. Therefore, this review aims to elucidate the mechanisms underlying current HER2-targeted therapy and explore a potential crosstalk with miRNAs, ultimately serving as a guide for the development of personalized therapeutic strategies."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer. (PubMed, N Engl J Med) - P3 | "In patients with high-risk, residual invasive HER2-positive breast cancer, postneoadjuvant T-DXd resulted in a significantly higher likelihood of invasive disease-free survival than T-DM1; toxic effects were mainly gastrointestinal and hematologic. An important identified risk of T-DXd is interstitial lung disease, which requires appropriate monitoring and management. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast05 ClinicalTrials.gov number, NCT04622319.)."

Journal • Breast Cancer • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

Clinical outcomes and treatment attrition rates of HER2 positive metastatic breast cancer (MBC) patients at a tertiary referral cancer centre in London: the Guy's Cancer experience. (SABCS 2025) - "Guy's Cancer serves one of the most ethnically diverse populations in the world. In this retrospective real-world study, 1st and 2nd line PFS was similar to published phase 3 studies. Although T-DXd appeared to perform better than T-DM1 in our population, it fell short of the outcomes seen in the DESTINY studies."

Clinical • Clinical data • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Trastuzumab Deruxtecan: Redefining Precision Oncology Across HER2-Driven Cancers. (PubMed, Crit Rev Oncol Hematol) - "In HER2-positive breast cancer, T-DXd significantly outperformed trastuzumab emtansine (T-DM1), with substantial improvements in progression-free and overall survival, while also showing benefit in HER2-low disease. The recent tumor-agnostic FDA approval highlights its broad clinical potential across solid tumors. This review summarizes the mechanism of action, pivotal clinical evidence, and emerging applications of T-DXd, underscoring its transformative role in modern oncology and outlining future prospects for combination strategies, biomarker-driven patient selection, and expanded global access."

Journal • Review • Breast Cancer • Colorectal Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Real-world treatment patterns and outcomes in patients with HER2+ metastatic breast cancer after treatment with trastuzumab deruxtecan (T-DXd) in the US (SABCS 2025) - "The most common regimens received as the index LOT were trastuzumab + tucatinib + chemotherapy (TTC; 34.2%), other anti-HER2 (18.9%), trastuzumab + chemotherapy (12.7%), other (12.7%), margetuximab + chemotherapy (8.8%), trastuzumab emtansine (T-DM1; 6.6%), and anti-HER2 TKI + chemotherapy (6.1%). Treatment sequencing data suggest that TTC and other anti-HER2 therapies are being used in the post-T-DXd rw setting, though potential differences by line exist. This study demonstrates an ongoing and substantial unmet need for more effective treatments among patients with HER2+ mBC previously treated with T-DXd, as shown by the short rwPFS/OS and short times on subsequent treatments following T-DXd."

Clinical • HEOR • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Real-world Clinical Outcomes in Patients with HER2+ Metastatic Breast Cancer Treated with Trastuzumab Deruxtecan After One or More Prior Lines of Therapy: Data from U.S Community Oncology Practices (SABCS 2025) - "Clinical outcomes of 1L and 2L rwTTF were examined in an exploratory subgroup of pts with 1L taxane+trastuzumab+pertuzumab based regimen (THP) followed by 2L T-DXd vs. 2L trastuzumab emtansine (T-DM1). The study findings affirm the real-world clinical effectiveness and safety of T-DXd in pts with HER2+ mBC as observed in the DESTINY clinical trials. Despite higher disease and comorbidity burden in this small sample of pts with 2L T-DXd use, longer delays in time to progression and discontinuation were observed compared to later line use of T-DXd; and longer rwTTF compared to 2L T-DM1 use, reinforcing the importance of utilizing T-DXd as early as possible in the treatment pathway to improve long-term pt outcomes."

Clinical • Clinical data • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients with high-risk human epidermal growth factor receptor 2-positive (HER2+) primary breast cancer (BC) with residual invasive disease after neoadjuvant therapy: Interim analysis of DESTINY-Breast05 (SABCS 2025) - P3 | "The additional analyses further characterize the positive benefit of T-DXd over T-DM1 in the post-neoadjuvant HER2+ BC residual disease setting, supporting T-DXd as a potential new standard-of-care in this setting. Timing of adjuvant RT did not impact incidence of adjudicated drug-related ILD with T-DXd. Additional results will be presented.Table."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Combinatory treatments of VRN101099 with antibody therapies for HER2-driven breast cancer (SABCS 2025) - "In BT474 or SKBR3, HER2 amplified breast cancer cells, xenograft models with subcutaneous or intracranial implantation, VRN101099 showed combinatory and synergistic anti-tumor effects with Trastuzumab, Pertuzumab, T-DM1, T-DXd, and Zanidatamab. The first-in-human dose escalation study of VRN101099 monotherapy will determine the maximal tolerable dose, and an optimal dose finding study for the combination will be followed."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • EGFR • HER-2

Impact of Prior T-DM1 Exposure on the Efficacy of Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer (SABCS 2025) - "Prior exposure to T-DM1 was associated with significantly shorter progression-free survival and a higher risk of disease progression following T-DXd treatment in patients with HER2-positive metastatic breast cancer. These findings highlight the potential impact of treatment sequencing on T-DXd efficacy and underscore the need for personalized therapeutic strategies in the advanced setting."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PGR