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    DRUG:

    Kadcyla (ado-trastuzumab emtansine)

    i
    Other names: RO5304020, PRO132365, R3502, RG 3502, RG3502, T-DM1, trastuzumab-DM1, trastuzumab-MCC-DM1, trastuzumab-mertansine, Herceptin-DM1
    Company:
    AbbVie, Roche
    Drug class:
    Microtubule inhibitor, HER2-targeted antibody-drug conjugate
    Related drugs:
    5d
    Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial. (PubMed, Lancet Oncol)
    Overall, GHS and quality of life were maintained for both treatment groups, with prespecified PRO variables favouring trastuzumab deruxtecan over treatment of physician's choice, suggesting that despite a longer treatment duration, there was no detrimental impact on patient health-related quality of life with trastuzumab deruxtecan. When considered with efficacy and safety data from DESTINY-Breast02, these results support the overall benefit of trastuzumab deruxtecan for patients with HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab emtansine.
    Clinical • P3 data • Clinical Trial,Phase III • Journal • Patient reported outcomes • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    lapatinib • Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • capecitabine
    6d
    A Study of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy (KATHERINE) (clinicaltrials.gov)
    P3, N=1487, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Apr 2025 --> May 2024
    Trial completion date
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    Herceptin (trastuzumab) • Kadcyla (ado-trastuzumab emtansine)
    10d
    NSABP FB-10: a phase Ib/II trial evaluating ado-trastuzumab emtansine (T-DM1) with neratinib in women with metastatic HER2-positive breast cancer. (PubMed, Breast Cancer Res)
    P1/2; The following biomarkers were associated with better outcomes for patients treated with T-DM1 + neratinib: (1) ctHER2-amp (C1D1) or in TP1; (2) Molecular Response scores; (3) loss of detectable ctDNA; (4) RNA levels of HER2; and (5) on-treatment loss of detectable ctHER2-amp. HER2 transcriptional and IHC/FISH status identify HER2-low cases (IHC 1+ or IHC 2+ and FISH negative) in these heavily anti-HER2 treated patients. Due to the small number of patients and samples in this study, the associations we have shown are for hypothesis generation only and remain to be validated in future studies. Clinical Trials registration NCT02236000.
    Journal • P1 data • P1/2 data • P2 data • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    Guardant360® CDx • Guardant360 Response™
    |
    Nerlynx (neratinib) • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine)
    14d
    Management of early-stage HER2-positive breast cancer and attitudes towards HER2DX test in Spain: insights from a nationwide survey. (PubMed)
    In the context of early-stage HER2+ breast cancer in Spain, a notable diversity in therapeutic approaches was observed. The majority of interviewed medical oncologists acknowledged HER2DX as a clinically valuable test for specific patients, in line with the 2022 SEOM-GEICAM-SOLTI clinical guidelines for early-stage breast cancer. To facilitate the full integration of HER2DX into clinical guidelines, conducting prospective studies to further validate its efficacy and utility was recommended.
    Journal
    |
    HER2DX
    |
    Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine)
    14d
    Antibody-drug conjugates in lung and breast cancer: Current evidence and future directions - a position statement from the ETOP IBCSG Partners Foundation. (PubMed, Ann Oncol)
    In lung cancer, trastuzumab deruxtecan (T-DXd) is approved in human epidermal growth factor receptor 2 (HER2)-mutated, unresectable or metastatic non-small cell lung cancer, with ADCs targeting HER3 (patritumab deruxtecan), trophoblast cell-surface antigen 2 (datopotamab deruxtecan and sacituzumab govitecan [SG]) and mesenchymal-epithelial transition factor (telisotuzumab vedotin) in late-stage clinical development. In breast cancer, several agents are already approved and widely used, including trastuzumab emtansine, T-DXd and SG, and multiple late-stage trials are ongoing...The ETOP IBCSG Partners Foundation are driving strong collaborations in this field and promoting the generation/sharing of databases, repositories and registries to enable greater access data. This will allow the most important research questions to be identified and prioritised, which will ultimately accelerate progress and help to improve patient outcomes.
    Review • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    EGFR mutation • HER-2 mutation
    |
    Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • patritumab deruxtecan (U3-1402) • Trodelvy (sacituzumab govitecan-hziy) • datopotamab deruxtecan (DS-1062a) • telisotuzumab vedotin (ABBV-399)
    16d
    Impact of concurrent antibody-drug conjugates and radiotherapy on symptomatic radiation necrosis in breast cancer patients with brain metastases: a multicenter retrospective study. (PubMed, J Neurooncol)
    This study suggests that concurrent ADC and radiotherapy are associated with a higher risk of SRN in HER2-positive breast cancer patients.
    Retrospective data • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    16d
    CyTOF analysis revealed platelet heterogeneity in breast cancer patients received T-DM1 treatment. (PubMed, Clin Immunol)
    These findings suggest that the expression of these platelet surface proteins may be correlated with the prognosis of T-DM1 treatment. These indicators offer valuable insights for predicting the therapeutic response to T-DM1 and may become important references in future clinical practice, contributing to a better understanding of the impact of ADC therapies and optimizing personalized cancer treatment strategies.
    Journal
    |
    CD36 (thrombospondin receptor) • CD9 (CD9 Molecule)
    |
    HER-2 positive
    |
    Kadcyla (ado-trastuzumab emtansine)
    20d
    PATRICIA: Study of Palbociclib and Trastuzumab With Endocrine Therapy in HER2-positive Metastatic Breast Cancer (clinicaltrials.gov)
    P2, N=73, Completed, SOLTI Breast Cancer Research Group | Active, not recruiting --> Completed
    Trial completion • Combination therapy • Metastases
    |
    HER-2 positive • HR positive
    |
    Prosigna™ Breast Cancer Prognostic Gene Signature Assay
    |
    Herceptin (trastuzumab) • Ibrance (palbociclib) • tamoxifen • Kadcyla (ado-trastuzumab emtansine) • capecitabine • fulvestrant • Halaven (eribulin mesylate) • Herceptin Hylecta (trastuzumab/hyaluronidase-oysk)
    20d
    Targeting HER2 in Gastroesophageal Adenocarcinoma: Molecular Features and Updates in Clinical Practice. (PubMed, Int J Mol Sci)
    However, unlike breast cancer, the efficacy of other anti-HER2 drugs, such as lapatinib, pertuzumab, and T-DM1, has failed to improve outcomes in advanced and locally advanced resectable GEA. Recently, the combination of trastuzumab with pembrolizumab, along with chemotherapy, and the development of trastuzumab deruxtecan, with its specific bystander activity, demonstrated improved outcomes, renewing attention in the treatment of this disease. This review will summarise historical and emerging therapies for the treatment of HER2-positive GEA, with a section dedicated to the HER2 molecular pathway and the use of novel blood biomarkers, such as circulating tumour DNA and circulating tumour cells, which may be helpful in the future to guide treatment decisions.
    Review • Journal • PD(L)-1 Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    Keytruda (pembrolizumab) • lapatinib • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    21d
    BOUQUET: A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors (clinicaltrials.gov)
    P2, N=550, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    ER (Estrogen receptor)
    |
    Avastin (bevacizumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • paclitaxel • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Verzenio (abemaciclib) • cyclophosphamide • letrozole • ipatasertib (RG7440) • triptorelin • goserelin acetate • giredestrant (GDC-9545) • inavolisib (GDC-0077)
    24d
    HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments. (PubMed, Cancers (Basel))
    HER2-targeting agents, such as the tyrosine kinase inhibitor lapatinib, the antibody drug conjugate (ADC) trastuzumab-emtansine or dual HER2 inhibition (pertuzumab and trastuzumab), have been investigated in the second-line setting but led to negative study results. More recently, the ADC trastuzumab-deruxtecan was authorized after the failure of trastuzumab-based treatment. However, further improvements in HER2-directed therapy are required as resistance mechanisms and HER2 heterogeneity limit the existing treatment options. This review aims to give an overview of the current standard-of-care HER2-directed therapy in gastric cancer, as well as its challenges and future developments.
    Review • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    lapatinib • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    28d
    Telangiectasias induced by combination tucatinib and ado-trastuzumab emtansine in a patient with metastatic breast cancer. (PubMed, Breast Dis)
    We postulate that telangiectasias may be a previously unreported dermatologic side effect of combination treatment with tucatinib and T-DM1. Electrocautery is a safe and effective procedure to reduce the appearance of telangiectasias and improve patient satisfaction during chemotherapy.
    Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive • EGFR positive
    |
    Kadcyla (ado-trastuzumab emtansine) • Tukysa (tucatinib)
    30d
    Testing Ado-Trastuzumab Emtansine as a Potential Targeted Treatment in Cancers With HER2 Genetic Changes (MATCH-Subprotocol Q) (clinicaltrials.gov)
    P2, N=38, Active, not recruiting, National Cancer Institute (NCI)
    Trial completion date
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 amplification
    |
    Kadcyla (ado-trastuzumab emtansine)
    1m
    Tucatinib Combination Treatment After Trastuzumab-Deruxtecan in Patients With ERBB2-Positive Metastatic Breast Cancer. (PubMed, JAMA Netw Open)
    Little is known regarding the outcomes associated with tucatinib combined with trastuzumab and capecitabine (TTC) after trastuzumab-deruxtecan exposure among patients with ERBB2 (previously HER2)-positive metastatic breast cancer (MBC)...The median number of prior treatment lines for metastatic disease at TTC treatment initiation was 4 (range, 2-15), including 82 patients (81.2%) with previous trastuzumab and/or pertuzumab and 94 (93.1%) with previous ado-trastuzumab-emtansine) exposure...In this study, TTC therapy was associated with clinically meaningful outcomes in patients with ERBB2-positive MBC after previous trastuzumab-deruxtecan treatment, including those with brain metastases. Prospective data on optimal drug sequencing in this rapidly changing therapeutic landscape are needed.
    Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • capecitabine • Tukysa (tucatinib)
    1m
    DS-8201a in Pre-treated HER2 Breast Cancer That Cannot be Surgically Removed or Has Spread [DESTINY-Breast02] (clinicaltrials.gov)
    P3, N=608, Active, not recruiting, Daiichi Sankyo | Trial completion date: Sep 2024 --> May 2025
    Trial completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive • HER-2 expression
    |
    lapatinib • Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • capecitabine
    1m
    Optimal Sequential Strategies for Antibody-Drug Conjugate in Metastatic Breast Cancer: Evaluating Efficacy and Cross-Resistance. (PubMed, Oncologist)
    The alternation of payload achieves different responses in different settings. T-Dxd followed by RC48 may be a potentially beneficial strategy in HER2-positive disease. Further research is needed to elucidate the mechanism of cross-resistance.
    Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • RB1 (RB Transcriptional Corepressor 1)
    |
    HER-2 positive • EGFR positive
    |
    Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Aidixi (disitamab vedotin) • Trodelvy (sacituzumab govitecan-hziy)
    1m
    Assessing the Efficacy and Safety of Anti-HER2 Therapy in Nigerian Women With HER2+ Breast Cancer Before and After Surgery (clinicaltrials.gov)
    P2, N=74, Not yet recruiting, University of Chicago
    New P2 trial
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    docetaxel • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • letrozole • goserelin acetate • Soltamox (tamoxifen citrate)
    1m
    Implementation of antibody-drug conjugates in HER2-positive solid cancers: Recent advances and future directions. (PubMed, Biomed Pharmacother)
    This review focuses on three approved anti-HER2 ADCs (T-DM1, DS-8201a, and RC48) and reviews ongoing clinical trials and failed trials based on anti-HER2 ADCs. Finally, we address the notable challenges linked to ADC development and underscore potential future avenues for tackling these hurdles.
    Review • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
    |
    HER-2 positive • HER-2 overexpression
    |
    Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Aidixi (disitamab vedotin)
    1m
    Biocompatible and Water-Soluble Shortwave-Infrared (SWIR)-Emitting Cyanine-Based Fluorescent Probes for In Vivo Multiplexed Molecular Imaging. (PubMed, ACS Appl Mater Interfaces)
    Furthermore, we demonstrate two-color SWIR fluorescence imaging of breast tumor apoptosis using an ICG-conjugated anticancer drug, Kadcyla and ICG-C9 or ICG-C11-conjugated annexin V. Finally, we show long-term (38 days) SWIR fluorescence imaging of breast tumor shrinkage induced by Kadcyla. This study provides a general strategy for multiplexed fluorescence molecular imaging with biocompatible and water-soluble SWIR-emitting cyanine probes.
    Preclinical • Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ANXA5 (Annexin A5)
    |
    Kadcyla (ado-trastuzumab emtansine)
    1m
    Charting the Course in Sequencing Antibody-Drug Conjugates in Breast Cancer. (PubMed, Biomedicines)
    Historically, trastuzumab emtansine (T-DM1) has been the most commonly used ADC for both early and metastatic HER2-positive disease. Considering the recent evidence related to trastuzumab deruxtecan (T-DXd), it is expected to assume the role of the main ADC in our clinical practice. Herein, we report a retrospective analysis of the sequence of different ADCs relying on available published data from clinical trials.
    Review • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Trodelvy (sacituzumab govitecan-hziy)
    1m
    A real-world study of treatment sequences and second-line clinical outcomes in patients with HER2-positive metastatic breast cancer in US community practice. (PubMed, Int J Clin Oncol)
    This real-world US study showed that approximately two-thirds of 2L patients received subsequent therapy and disease progression was the most common reason for 2L discontinuation highlighting the need for timely 2L treatment with the most efficacious drug to allow patients to achieve longer treatment duration and delayed progression.
    Clinical data • Journal • Real-world evidence • Real-world • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    2ms
    HER2CLIMB-02: A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer (clinicaltrials.gov)
    P3, N=565, Recruiting, Seagen Inc. | Trial completion date: Apr 2024 --> Oct 2027
    Trial completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    Kadcyla (ado-trastuzumab emtansine) • Tukysa (tucatinib)
    2ms
    Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib in Combination With Trastuzumab Deruxtecan or With Trastuzumab Emtansine and to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread (clinicaltrials.gov)
    P1/2, N=240, Not yet recruiting, Boehringer Ingelheim
    New P1/2 trial • Combination therapy • Metastases
    |
    Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • zongertinib (BI 1810631)
    2ms
    Effects of trastuzumab emtansine on canine urothelial carcinoma cells in vitro and in vivo. (PubMed, Vet Comp Oncol)
    Tumour volumes were significantly smaller in the T-DM1 group compared to the trastuzumab and vehicle control groups. These findings indicate that T-DM1 exerts a stronger antitumour effect than that of trastuzumab on canine UC cells in vitro and in vivo, possibly by inducing apoptosis due to DM1.
    Preclinical • Journal
    |
    ANXA5 (Annexin A5)
    |
    HER-2 expression
    |
    Kadcyla (ado-trastuzumab emtansine)
    2ms
    ProHer: A Study to Evaluate Patient Preference for Home Administration of Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Administration in Participants With Early or Locally Advanced/Inflammatory HER2-Positive Breast Cancer (clinicaltrials.gov)
    P3, N=347, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Sep 2025 --> Dec 2025 | Trial primary completion date: Aug 2024 --> Mar 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 amplification • EGFR positive
    |
    Herceptin (trastuzumab) • carboplatin • paclitaxel • docetaxel • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • doxorubicin hydrochloride • cyclophosphamide • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
    2ms
    A Study Comparing BL-M07D1 With T-DM1 in Patients With Unresectable Locally Advanced or Metastatic HER2-positive Breast Cancer (clinicaltrials.gov)
    P3, N=268, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.
    New P3 trial • Metastases
    |
    Kadcyla (ado-trastuzumab emtansine) • BL-M07D1
    2ms
    SCHOLAR-2: Safety of Continuing HER-2 Directed Therapy in Overt Left Ventricular Dysfunction (clinicaltrials.gov)
    P2, N=130, Recruiting, Population Health Research Institute | Trial completion date: Dec 2025 --> Jun 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    Herceptin (trastuzumab) • docetaxel • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • Herzuma (trastuzumab-pkrb) • Trazimera (trastuzumab-qyyp)
    2ms
    DP303c Versus Trastuzumab Emtansine in in Patients With HER2-positive Advanced Breast Cancer (clinicaltrials.gov)
    P3, N=442, Not yet recruiting, CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
    New P3 trial • Metastases
    |
    Kadcyla (ado-trastuzumab emtansine) • trastuzumab envedotin (DP303c)
    2ms
    Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial. (PubMed, Nat Commun)
    Patients (female; n = 329; randomized 2:1) received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year. Limitations include the lack of ado-trastuzumab emtansine as an option for patients with residual disease and the descriptive nature of the secondary, long-term efficacy endpoints. PEONY confirms the positive benefit:risk ratio of neoadjuvant/adjuvant pertuzumab, trastuzumab, and docetaxel treatment in this patient population.
    P3 data • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    docetaxel • 5-fluorouracil • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • cyclophosphamide • epirubicin
    2ms
    PHERGAIN-2: Chemotherapy-Free pCR-Guided Strategy With Trastuzumab-pertuzumab and T-DM1 in HER2-positive Early Breast Cancer (clinicaltrials.gov)
    P2, N=393, Active, not recruiting, MedSIR | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
    |
    tamoxifen • Kadcyla (ado-trastuzumab emtansine) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
    2ms
    Stereotactic Radiation Therapy for HE2-positive Oligometastatic Breast Cancer (clinicaltrials.gov)
    P=N/A, N=58, Recruiting, N.N. Petrov National Medical Research Center of Oncology
    New trial • Pan tumor • Metastases
    |
    Kadcyla (ado-trastuzumab emtansine)
    2ms
    Clinical Outcomes of Patients with HER2 Positive Metastatic Breast Cancer to the Brain, with First-Line Trastuzumab, Pertuzumab and Chemotherapy, in a Real-World Setting. (PubMed, Breast Cancer (Dove Med Press))
    All patients initiated a combination treatment of trastuzumab, pertuzumab, and chemotherapy (TPC), and 72% moved to second-line treatment during the study follow-up period (82% ado-trastuzumab emtansine). Patients with upfront brain involvement at the time of mBC diagnosis had shorter survival compared to those who started TPC without brain metastases. Nonetheless, the overall results from this study compare favorably with previous studies and contribute to understanding the value of traditional treatment options, which will serve as a baseline for future treatment strategies in the real-world setting.
    Clinical data • Journal • Real-world evidence • Real-world • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive • HR positive • EGFR positive
    |
    Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine)
    2ms
    Evidence for cytoprotective autophagy in response to HER2-targeted monoclonal antibodies. (PubMed, J Pharmacol Exp Ther)
    In this review, we provide an overview of the autophagic machinery induced in response to HER2-targeted monoclonal antibodies, with a focus on trastuzumab and trastuzumab-emtansine, in an effort to determine whether autophagy targeting or modulation could be translated clinically to increase their effectiveness and/or overcome resistance development...This series designed in an attempt to build a conclusion whether autophagy targeting or modulation is an effective adjuvant strategy to increase the efficacy of chemotherapeutic agents. In this review, we shed the light on the relationship between the autophagic machinery and HER2 targeted therapies.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 overexpression
    |
    Kadcyla (ado-trastuzumab emtansine)
    2ms
    MyTACTIC: A Study Evaluating Targeted Therapies in Participants Who Have Advanced Solid Tumors With Genomic Alterations or Protein Expression Patterns Predictive of Response (clinicaltrials.gov)
    P2, N=252, Completed, Genentech, Inc. | Active, not recruiting --> Completed
    Trial completion • Tumor mutational burden • Metastases
    |
    Tecentriq (atezolizumab) • Rozlytrek (entrectinib) • paclitaxel • docetaxel • Alecensa (alectinib) • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • capecitabine • Gavreto (pralsetinib) • Tukysa (tucatinib) • ipatasertib (RG7440) • inavolisib (GDC-0077) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf) • tiragolumab (RG6058)
    2ms
    Palbociclib in Estrogen Receptor Positive (ER+) Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Metastatic Breast Cancer (clinicaltrials.gov)
    P1/2, N=3, Terminated, University of Kansas Medical Center | Active, not recruiting --> Terminated; Low accrual
    Trial termination • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • EGFR positive
    |
    Ibrance (palbociclib) • Kadcyla (ado-trastuzumab emtansine) • letrozole
    2ms
    Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial (clinicaltrials.gov)
    P1, N=2, Terminated, OHSU Knight Cancer Institute | Active, not recruiting --> Terminated; Low accrual
    Trial termination
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • Avastin (bevacizumab) • Venclexta (venetoclax) • Lynparza (olaparib) • Mekinist (trametinib) • erlotinib • Gilotrif (afatinib) • Yervoy (ipilimumab) • Ibrance (palbociclib) • dasatinib • Zelboraf (vemurafenib) • Tafinlar (dabrafenib) • carboplatin • Imfinzi (durvalumab) • sorafenib • Rozlytrek (entrectinib) • imatinib • sunitinib • everolimus • Nerlynx (neratinib) • Iclusig (ponatinib) • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Lorbrena (lorlatinib) • Lenvima (lenvatinib) • bortezomib • doxorubicin hydrochloride • capecitabine • Verzenio (abemaciclib) • Xtandi (enzalutamide capsule) • Cabometyx (cabozantinib tablet) • albumin-bound paclitaxel • Stivarga (regorafenib) • abiraterone acetate • oxaliplatin • Aliqopa (copanlisib) • Vizimpro (dacomitinib) • Zydelig (idelalisib) • daunorubicin • Zolinza (vorinostat) • Idhifa (enasidenib) • Farydak (panobinostat) • Erivedge (vismodegib) • Nubeqa (darolutamide) • bicalutamide • leucovorin calcium • cabazitaxel • Vesanoid (tretinoin) • fluorouracil topical
    2ms
    Phase Ib Dose-escalation Trial of Taselisib (GDC-0032) in Combination With Anti-HER2 Therapies in Participants With Advanced HER2+ Breast Cancer (clinicaltrials.gov)
    P1, N=68, Active, not recruiting, Otto Metzger, MD | Trial completion date: Dec 2023 --> May 2024
    Trial completion date • Combination therapy • Metastases
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    HER-2 (Human epidermal growth factor receptor 2)
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    Herceptin (trastuzumab) • paclitaxel • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • taselisib (GDC-0032)
    2ms
    Addressing Residual Disease in HER2-Positive and Triple-Negative Breast Cancer: What Is Next? (PubMed, Curr Oncol Rep)
    Patients with TNBC with residual disease after neoadjuvant therapy can be treated with pembrolizumab, capecitabine, or olaparib. Those with HER2-positive disease are treated with adjuvant trastuzumab emtansine. The treatment of early breast cancer has evolved significantly, and patient outcomes continue to improve. As better treatments are developed, we will need biomarkers to determine which patients may benefit from certain therapies to continue to improve outcomes by right-sizing treatments and limiting toxicities.
    Review • Journal • PARP Biomarker • PD(L)-1 Biomarker
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    HER-2 (Human epidermal growth factor receptor 2)
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    HER-2 positive • EGFR positive
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    Keytruda (pembrolizumab) • Lynparza (olaparib) • Kadcyla (ado-trastuzumab emtansine) • capecitabine
    3ms
    Copper Cu 64-DOTA-Trastuzumab PET in Predicting Response to Treatment With Ado-Trastuzumab Emtansine in Patients With Metastatic HER2 Positive Breast Cancer (clinicaltrials.gov)
    P=N/A, N=10, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024
    Trial completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    Herceptin (trastuzumab) • Kadcyla (ado-trastuzumab emtansine)
    3ms
    A Study to Compare DB-1303/BNT323 Versus T-DM1 in Breast Cancer (clinicaltrials.gov)
    P3, N=224, Recruiting, DualityBio Inc.
    New P3 trial • Metastases
    |
    Kadcyla (ado-trastuzumab emtansine) • BNT323
    3ms
    Comparison of trastuzumab emtansine, trastuzumab deruxtecan, and disitamab vedotin in a multiresistant HER2-positive breast cancer lung metastasis model. (PubMed, Clin Exp Metastasis)
    L-JIMT-1 cells were resistant to all five tyrosine kinase inhibitors tested in vitro (afatinib, erlotinib, lapatinib, sapitinib, and tucatinib). In a mouse model, all three ADCs inhibited the growth of L-JIMT-1 lung metastases compared to a vehicle, but DV and T-DXd more strongly than T-DM1, and DV treatment led to the smallest tumor burden. The L-JIMT breast cancer lung metastasis model developed may be useful in the evaluation of anti-cancer agents for multiresistant HER2-positive advanced breast cancer.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive • EGFR expression
    |
    erlotinib • Gilotrif (afatinib) • lapatinib • Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Tukysa (tucatinib) • Aidixi (disitamab vedotin) • sapitinib (AZD8931)
    3ms
    Estimating Public Economic Gains from Early Breast Cancer and Curative Treatment: A Case Study in Human Epidermal Growth Factor Receptor (HER-2) Positive Targeted Therapies. (PubMed, Oncol Ther)
    Women diagnosed with HER2-positive eBC were estimated to pay less lifetime gross taxes and receive more in sickness benefits compared with healthy women. Treatments that improve outcomes are likely to offer fiscal gains for government from improved work force participation.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
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    HER-2 positive • EGFR positive
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    Kadcyla (ado-trastuzumab emtansine)