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

Revolutionizing breast cancer treatment: the promise of antibody-drug conjugates. (PubMed, Clin Adv Hematol Oncol) - "Currently, 4 ADCs-sacituzumab govitecan, trastuzumab deruxtecan, trastuzumab emtansine, and the more-recent datopotamab deruxtecan-are approved for clinical application, with several others in advanced stages of development. Additionally, biomarker-driven strategies to identify those patients most likely to benefit from ADC therapy will support more personalized approaches to treatment. This review explores the structural and mechanistic features of ADCs in breast cancer, highlighting their therapeutic potential, and discusses ongoing clinical trials exploring new-generation ADCs and combination therapies."

Journal • Review • Breast Cancer • Oncology • Solid Tumor

Quantification of total trastuzumab (TTM) concentrations in blood samples from patients treated with trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-Dxd) (ESMO 2025) - No abstract available

Clinical • Oncology

DS-8201a Versus T-DM1 for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [DESTINY-Breast03] (clinicaltrials.gov) - P3 | N=524 | Active, not recruiting | Sponsor: Daiichi Sankyo | Trial completion date: Jun 2025 ➔ Nov 2025

Trial completion date • Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Antibody-drug conjugates for treating early-stage breast cancer: current use, anticipated evolutions. (PubMed, NPJ Breast Cancer) - "After improving outcomes for patients with metastatic disease, ADC testing moved to the curative setting, where already one agent (trastuzumab emtansine) has been approved, after demonstrating to improve overall survival. Herein, we review the rationale, evidence, and challenges with the use of ADCs in the early-stage setting."

Journal • Review • Breast Cancer • Oncology • Solid Tumor

CAM Assay: An Alternative, 3Rs-compliant, In Vivo Model for the Development of Anticancer Immunotherapies (EACR 2025) - "A treatment with different immunotherapy reagents is performed between EDD10 and EDD18: monoclonal Abs (bevacizumab, trastuzumab, rituximab) in 4 doses; ADC (trastuzumab emtansine) in 1 dose; ICIs (pembrolizumab, nivolumab, atezolizumab, avelumab) in 5 doses; tumor cell based vaccine (STC1010) in 3 doses; CAR-T cells & CAR-NK cells in 1 dose. Our work demonstrates that the CAM assay is suitable for testing different IO anticancer treatments. The presence of an active immune system allows a suitable characterization of the effects of immunotherapy reagents on tumor cells, the microenvironment, and the entire organism. As one part of New Approach Methodologies (NAMs), the CAM assay provides a relevant alternative, 3Rs-compliant, in vivo model for testing novel immunotherapies on a large spectrum of cancer types, as a monotherapy or as an in combination approach."

IO biomarker • Preclinical • Oncology

Phase II clinical trial of trastuzumab emtansine for HER2-positive advanced extramammary Paget's disease (TEMENOS-2) (ESMO 2025) - No abstract available

Clinical • Metastases • P2 data • Oncology • HER-2

Evaluating Trastuzumab Emtansine in Residual Invasive HER2-Positive Breast Cancer: A Meta-Analysis of Randomized Controlled Trials (ESMO 2025) - No abstract available

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

HER2-Driven Breast Cancer: Role of the Chaperonin HSP90 in Modulating Response to Trastuzumab-Based Therapeutic Combinations. (PubMed, Int J Mol Sci) - "In HER2+ breast cancer models (AU565, BT474, MCF7-HER2), HER2 downregulation induced HSP90 upregulation and growth inhibitory synergism between trastuzumab and docetaxel...Conversely, HSP90 downregulation blunted the therapeutic response to trastuzumab/pertuzumab/tamoxifen or trastuzumab-emtansine. In HER2+ breast cancer patients, high HSP90 expression was associated with significant progression-free survival benefit with the triple combination, as compared with trastuzumab and chemotherapy, although the interaction test was not statistically significant. Overall, our results highlight a mechanistic role for HSP90 in determining the response of breast cancer cells to HER2-targeted agents and suggest that trastuzumab/pertuzumab combinations may be particularly advantageous in HSP90-high, HER2+ breast cancer."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDC37 • HER-2 • HSP90AA1

Comprehensive genomic profiling to guide personalized targeted and immunotherapy in gastrointestinal tumors: Subgroup analysis of the ROME trial (ESMO-GI 2025) - P2 | "Funding: Erlotinib, Pertuzumab, Vemurafenib, Trastuzumab Emtansine, Alectinib, Vismodegib, Cobimetinib, Atezolizumab, Trastuzumab, Ipatasertib (GDC-0068), Entrectinib and Pralsetinib were provided by Roche; Everolimus, Lapatinib, Alpelisib were provided by Novartis, Palbociclib and Talazoparib were provided by Pfizer, Ipilimumab and Nivolumab were provided by Bristol Myers Squibb (BMS); Brigatinib was provided by Takeda Pharmaceutical Co.; Ponatinib, Itacitinib (INCB039110), Pemigatinib (INCB054828) were provided by Incyte; Selpercatinib was provided by Eli Lilly; Tepotinib was provided by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). CGP with MTB-guided TT may identify patients with GI cancer who benefit from targeted therapies not routinely available in clinical practice. The roles of TMB and potential disease-specific thresholds deserve further investigation."

IO biomarker • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • TMB

ProTarget - A Danish Nationwide Clinical Trial on Targeted Cancer Treatment Based on Genomic Profiling (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Ulrik Lassen | Trial completion date: Apr 2025 ➔ Apr 2030 | Trial primary completion date: Apr 2024 ➔ Apr 2029

Trial completion date • Trial primary completion date • Oncology

Clinical characteristics, treatment, and survival of thrombocytopenia induced by T-DM1 in early HER2-positive breast cancer. (PubMed, Front Oncol) - "Postmenopausal status correlated with an increased risk of platelet count decrease. Different platelet-producing drugs demonstrated comparable effectiveness in managing thrombocytopenia."

Journal • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Thrombocytopenia • HER-2

Trastuzumab Emtansine (T-DM1)-Induced Porto-Sinusoidal Vascular Disorder: A Case Report. (PubMed, Cureus) - "She remained asymptomatic and with no evidence of disease for seven months. T-DM1-related PSVD is a rare complication of T-DM1 treatment that should not be overlooked. Clinical suspicion is essential for diagnosis, and T-DM1 suspension is the only known treatment."

Journal • Breast Cancer • Cardiovascular • Hepatology • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hypertension • Oncology • Otorhinolaryngology • Portal Hypertension • Solid Tumor • HER-2

Rechallenge with anti-HER2 regimens in metastatic colorectal cancer: The retrospective RHEA study (ESMO-GI 2025) - P2 | "Anti-HER2 rechallenge was performed with TDM-1 (NCT03418558) (n=9), trastuzumab-deruxtecan (NCT03384940, NCT04744831) (n=7), trastuzumab/lapatinib (n=6), trastuzumab/pertuzumab (n=3), or pertuzumab/TDM-1 (n=1)...Among 6 responders, 3 had received trastuzumab deruxtecan, 2 trastuzumab/lapatinib, and 1 T-DM1, all displaying HER2 3+ tumors at baseline and maintained at rebiopsy when available (n=5)... Rechallenge with an anti-HER2 therapy led to further responses in about ¼ chemorefractory, anti-HER2 heterogeneously pretreated, mCRC patients. PR at rechallenge were observed, but not limited, to trastuzumab-deruxtecan and confined to retained IHC 3+. Further translational studies are needed to better select molecular characteristics underlying clinical outcome."

Metastases • Retrospective data • Colorectal Cancer • Oncology • Solid Tumor • BRAF

Long Durable Response With Trastuzumab Deruxtecan Monotherapy in a Triple-Negative Metastatic Breast Cancer Patient With Human Epidermal Growth Factor Receptor 2 Mutation: A Long-Term Follow-Up and Literature Review. (PubMed, J Med Cases) - "ADCs approved for breast cancer include trastuzumab emtansine (Kadcyla, T-DM1) and trastuzumab deruxtecan (Enhertu, T-DXd)...This case makes a compelling argument for considering HER2-targeted therapies, mainly ADCs, in HER2-mutant breast cancer patients either as a monotherapy or in combination with other therapies, particularly in metastatic disease. This case report also indicates that further research and clinical trials looking into the efficacy and safety profile of anti-HER2 treatments in HER2-mutant breast cancers are warranted."

Journal • Monotherapy • Breast Cancer • Endometrial Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Current research status on HER2 protein expression levels and the efficacy of targeted therapy in breast cancer. (PubMed, Front Oncol) - "In patients with HER2-positive breast cancer, the efficacy of T-DM1 is independent of HER2 protein expression levels. Patients with different HER2 expression levels can benefit from T-DXd treatment, with a potential positive correlation with HER2 expression levels...However, high-level evidence to evaluate the relationship between HER2 expression levels and the efficacy of different targeted therapies is lacking. Determining whether HER2 protein expression levels influence treatment outcomes and whether tailored strategies based on HER2 protein expression levels should be implemented holds significant implications for advancing precision medicine in breast cancer."

Biomarker • Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Porto-Sinusoidal Vascular Liver Disease Associated With Trastuzumab Emtansine: A Case Report. (PubMed, Cureus) - "Porto-sinusoidal vascular disorder (PSVD) is a rare vascular liver disease characterised by alterations in the portal and sinusoidal vasculature in the absence of cirrhosis, often associated with immune conditions, haematological disorders, or medication exposure. The patient was treated with diuretics and lactulose, with marked clinical improvement and no further complications over one year of follow-up. This case underscores the importance of considering PSVD in patients with unexplained liver dysfunction and portal hypertension following cancer therapy."

Journal • Breast Cancer • Cardiovascular • CNS Disorders • Fibrosis • Hematological Disorders • Hepatic Encephalopathy • Hepatology • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hypertension • Immunology • Liver Failure • Oncology • Portal Hypertension • Solid Tumor • Thrombocytopenia • HER-2

Elective arteriovenous fistula ligation for prevention of lymphedema in a patient with breast cancer before ipsilateral axillary lymph node dissection: A case report. (PubMed, Oncol Lett) - "As of March 2025, the kidney graft function was stable (estimated glomerular filtration rate, 56.9 ml/min/1.73 m2) and second-line treatment with trastuzumab emtansine was terminated after 3 months due to symptomatic brain metastases. The upfront ligation of AVF located in the antecubital fossa decreased the risk of upper limb LE, which may occur during BC treatment, ALND and chest wall and axillary region radiotherapy."

Journal • Breast Cancer • Cardiovascular • Chronic Kidney Disease • HER2 Positive Breast Cancer • Nephrology • Oncology • Palliative care • Renal Disease • Solid Tumor • Transplantation • HER-2

Long-term survival in a patient with brain metastases and leptomeningeal disease of breast cancer: a case report of a patient receiving trastuzumab-deruxtecan. (PubMed, Arch Gynecol Obstet) - "Long-term survival is achievable in patients with CNS metastases from BC, even in the presence of leptomeningeal disease, especially with the use of targeted therapies like T-DXd."

Journal • Breast Cancer • CNS Tumor • Epilepsy • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

HER2-targeted agents and interstitial lung disease: A real-world pharmacovigilance analysis using FAERS data. (PubMed, J Oncol Pharm Pract) - "However, only two cases of ILD were associated with neratinib. The overall median time-to-onset was 75.5 days (interquartile range: 27.0-163.0). Logistic regression analysis revealed that elderly patients, treatment with T-Dxd, and treatment for non-breast cancer were significant risk factors for fatal outcomes related to ILD associated with HER2-targeted agents.ConclusionThis study suggests a significant association between the ILD and HER2-targeted agents, including T-Dxd, T-DM1, pertuzumab, trastuzumab, tucatinib, and lapatinib."

Adverse events • Journal • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

Drug-tolerant persisting polyploid giant cancer cells mediate resistance to HER2-targeting antibody-drug conjugates. (PubMed, Cancer Lett) - "HER2-positive breast cancer (JIMT-1) and gastric cancer (MKN7, SNU-216) cells were treated with HER2-directed ADCs, trastuzumab emtansine, trastuzumab deruxtecan, XMT-1522, and disitamab vedotin (DV)...Drug-tolerant PGCCs upregulated nectin-4, and treatment with enfortumab vedotin, a nectin-4-targeted ADC, inhibited the regrowth of JIMT-1 xenografts. ADC treatment induces PGCCs that contribute to drug resistance. ADC-induced drug-tolerant PGCCs express nectin-4, which may serve as a potential therapeutic target."

Journal • Breast Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • NECTIN4

Antibody-drug conjugates in breast cancer: Resistance mechanisms and prospects (PubMed, Bull Cancer) - "Despite significant advances with agents such as trastuzumab emtansine, sacituzumab govitecan and trastuzumab deruxtecan, resistance mechanisms limit their efficacy. Despite these advances, challenges remain, notably in identifying biomarkers of response and defining the optimal therapeutic sequence to avoid cross-resistance. Ongoing research is aimed at refining the use of ADCs to maximize their efficacy and prolong the survival of breast cancer patients."

IO biomarker • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ERBB3 • HER-2 • TACSTD2

Comparison of T-DM1 and trastuzumab-pertuzumab in HER2-positive breast cancer patients with residual disease after neoadjuvant therapy: a retrospective study. (PubMed, World J Surg Oncol) - "In patients with HER2-positive early breast cancer who have residual disease after receiving neoadjuvant treatment with HP, the continued administration of HP can achieve therapeutic effects comparable to those of T-DM1, without significant complications."

Clinical • Journal • Retrospective data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Thrombocytopenia • HER-2

Overcoming Antibody-Drug Conjugate Resistance in HER2-Positive Breast Cancer: Insights into Molecular Mechanisms and Targeted Therapeutic Approaches (EACR 2025) - "Second-generation antibody-drug conjugates (ADC) trastuzumab deruxtecan (T-DXd; Enhertu®) and trastuzumab duocarmazine (SYD985) have shown effectiveness in HER2-positive and HER2-low metastatic breast cancer...BT-474 and MDA-MB-361 resistant cells retained sensitivity to the ADC trastuzumab emtansine and the tyrosine kinase inhibitors neratinib and lapatinib... Our study provides insight into the molecular basis of ADC resistance, identifying potential targets to overcome resistance and enhance ADC efficacy in HER2-positive breast cancer. The identification of RET downregulation in resistant cells and the observed synergy between T-DXd and selpercatinib highlight a potential strategy for limiting T-DXd resistance."

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

DESTINY-Breast01: A Study of DS-8201a in Metastatic Breast Cancer Previously Treated With Trastuzumab Emtansine (T-DM1) (clinicaltrials.gov) - P2 | N=253 | Terminated | Sponsor: Daiichi Sankyo | Completed ➔ Terminated; The last participant was transitioned to alternative study.

Trial termination • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread (clinicaltrials.gov) - P1/2 | N=582 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Aug 2028 ➔ Sep 2029 | Trial primary completion date: Feb 2027 ➔ Sep 2029

Trial completion date • Trial primary completion date • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor