Novel Non–HER2-targeted Therapies in HER2+ Breast Cancer

2019 ◽  
pp. 179-212
Author(s):  
Marina N. Sharifi ◽  
Ruth M. O'Regan
Keyword(s):  
Breast Cancer ◽  
Targeted Therapies ◽  
Her2 Breast Cancer

Incorporating HER2/HER3 targeted therapies across solid tumors: Assessing the impact of digital education on clinician practice patterns.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11036-11036
Author(s):  
Tariqa Ackbarali ◽  
Wendy Turell ◽  
Elizabeth L. del Nido ◽  
Adam Brufsky ◽  
Stephen V. Liu
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Clinical Practice ◽  
Patient Experience ◽  
Targeted Therapies ◽  
Her2 Breast Cancer ◽  
Treatment Plans ◽  
Tumor Types ◽  
Behavioral Impact

11036 Background: Improved understanding of the interactions between HER2 and HER3, the heterogeneity of HER-expressing disease, and mechanisms of resistance to anti-HER2 therapy has led to increasing number of treatment options to address clinical needs. Tumor types of interest, impacted by HER2/HER3 expression and pathophysiology were breast cancer, non-small cell lung cancer (NSCLC), gastric cancer, and colorectal cancer (CRC). Increasing competency in these areas is deemed critical to clinician’s ability to individualize treatment plans and improve patient outcomes. Methods: A 2-hour CME activity was broadcast live-online in September 2020 and remains on-demand through September 2021 at OMedLive.com. The educational initiative was divided into one hour addressing HER2 and HER3, testing guidelines, resistance mechanisms and emerging data elucidating recent and ongoing clinical trials across NSCLC, gastric cancer, and CRC. The second hour focused on individualizing metastatic HER2+ breast cancer, HER2-low breast cancer as an emerging subtype, and management of side effects. Knowledge and competence questions were administered pre-, immediate post-, and 2 mos. post-activity. Behavioral impact questions were also asked at follow-up. Data from these questions were analyzed to determine engagement and clinical impact. Results: To date, 448 clinicians participated in the activity. Across the seven CME test questions, improvements in knowledge and competence were observed in the clinical applications of HER2-directed agents and HER3 antibody drug conjugates (ADCs), first-line standard of care for HER2+ breast cancer, and adverse event management for HER2 ADCs. At 2-mos. follow-up, 67% reported improved behavioral impact on both clinical practice and patient experience and outcomes. Clinicians provided specific write-in examples of these changes, noting improved patient-reported outcomes, improved treatment adherence, improved competence developing treatment plans, and increased understanding of HER2/HER3 pathophysiology. Updated and expanded results will be shared. Conclusions: The activity was successful in improving clinician understanding of the relationship between HER2/HER3, pathophysiology across tumor types, and applications of emerging targeted therapies. Open-ended responses to behavioral impact questions illustrated clear improvements in clinician-reported patient experience and outcomes, clinical practice management, and knowledge of emerging HER2/HER3 therapies and their uses across multiple solid tumors.

A phase III, multicenter, randomized, open label trial of [fam-] trastuzumab deruxtecan (DS-8201a) versus investigator’s choice in HER2-low breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS1102-TPS1102 ◽  
Author(s):  
Shanu Modi ◽  
Shoichiro Ohtani ◽  
Caleb C. Lee ◽  
Kongming Wang ◽  
Kapil Saxena ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapies ◽  
Topoisomerase I ◽  
Bystander Effect ◽  
Phase 1 ◽  
Objective Response ◽  
Phase Iii ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Her2 Breast Cancer

TPS1102 Background: Human epidermal growth factor receptor 2 (HER2)-targeted therapies have greatly improved survival in HER2+ breast cancer (BC). However, there are many more BC patients with HER2-low expression (immunohistochemistry [IHC] 1+ or 2+/ in situ hybridization-negative), for whom no HER2-targeted therapies are approved. [Fam-] trastuzumab deruxtecan (T-DXd; formerly DS-8201a) is an antibody-drug conjugate with a humanized HER2 antibody, peptide-based cleavable linker, and a topoisomerase I inhibitor payload. It has a drug-to-antibody ratio of ~8 and the membrane permeability of the cleaved payload enables a cytotoxic bystander effect. In an ongoing phase 1 trial, T-DXd demonstrated an objective response rate (ORR) of 44.2% (19/43) with a manageable safety profile in heavily pretreated, advanced HER2-low BC (Oct 2018 data cutoff; Modi et al, SABCS 2018). Methods: DESTINY-Breast04 is a randomized, phase 3, 2-arm, open-label, multicenter study comparing efficacy and safety of T-DXd vs physician’s choice in HER2-low, unresectable and/or metastatic BC. Approximately 540 subjects will be randomized 2:1 to T-DXd (5.4 mg/kg intravenous every 3 weeks) or physician’s choice (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel). Randomization is stratified by HER2 IHC status, number of prior treatments, and prior CDK4/6 inhibitor therapy/hormone receptor (HR) status. HER2 IHC will be assessed and confirmed by central testing based on archival samples. The primary efficacy endpoint is progression-free survival (PFS) per mRECIST v1.1 determined by blinded independent central review. Secondary efficacy endpoints are investigator-assessed PFS, overall survival, confirmed ORR, and duration of response. Safety endpoints include serious adverse events (AEs), treatment-emergent AEs, and AEs of special interest (interstitial lung disease/pneumonitis, cardiotoxicity, and infusion-related reactions). Primary PFS analysis will occur when 318 events are observed in HR+ subjects; providing 90% power to detect a hazard ratio of 0.68 with 1-sided α of 0.025. Enrollment began in Dec 2018. Clinical trial information: NCT03734029.

scholarly journals Cancer Vaccines, Treatment of the Future: With Emphasis on HER2-Positive Breast Cancer

2021 ◽  
Vol 22 (2) ◽  
pp. 779
Author(s):  
Sandeep Pallerla ◽  
Ata ur Rahman Mohammed Abdul ◽  
Jill Comeau ◽  
Seetharama Jois
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Targeted Therapies ◽  
Cancer Vaccines ◽  
Vaccine Therapy ◽  
Current Status ◽  
Breast Cancer Patients ◽  
Therapeutic Vaccines ◽  
Advantages And Disadvantages ◽  
Her2 Breast Cancer

Breast cancer is one of the leading causes of death in women. With improvements in early-stage diagnosis and targeted therapies, there has been an improvement in the overall survival rate in breast cancer over the past decade. Despite the development of targeted therapies, tyrosine kinase inhibitors, as well as monoclonal antibodies and their toxin conjugates, all metastatic tumors develop resistance, and nearly one-third of HER2+ breast cancer patients develop resistance to all these therapies. Although antibody therapy has shown promising results in breast cancer patients, passive immunotherapy approaches have limitations and need continuous administration over a long period. Vaccine therapy introduces antigens that act on cancer cells causing prolonged activation of the immune system. In particular, cancer relapse could be avoided due to the presence of a longer period of immunological memory with an effective vaccine that can protect against various tumor antigens. Cancer vaccines are broadly classified as preventive and therapeutic. Preventive vaccines are used to ward off any future infections and therapeutic vaccines are used to treat a person with active disease. In this article, we provided details about the tumor environment, different types of vaccines, their advantages and disadvantages, and the current status of various vaccine candidates with a focus on vaccines for breast cancer. Current data indicate that therapeutic vaccines themselves have limitations in terms of efficacy and are used in combination with other chemotherapeutic or targeting agents. The majority of breast cancer vaccines are undergoing clinical trials and the next decade will see the fruitfulness of breast cancer vaccine therapy.

scholarly journals Melatonin potentiates the cytotoxic effect of Neratinib in HER2+ breast cancer through promoting endocytosis and lysosomal degradation of HER2

Oncogene ◽  
2021 ◽  
Author(s):  
Zundong Liu ◽  
Xiaolin Sang ◽  
Min Wang ◽  
Yichao Liu ◽  
Jiao Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapies ◽  
Inhibitory Effect ◽  
Breast Cancers ◽  
Lysosomal Degradation ◽  
Her2 Protein ◽  
Her2 Breast Cancer ◽  
Her2 Signaling ◽  
Chaperone Complex

AbstractComplete blockade of the HER2 protein itself and HER signaling network is critical to achieving effective HER2-targeted therapies. Despite the success of HER2-targeted therapies, the diseases will relapse in a significant fraction of patients with HER2+ breast cancers. How to improve the therapeutic efficacy of existing HER2-targeted agents remains an unmet clinical need. Here, we uncover a role of Melatonin in diminishing HER2-mediated signaling by destruction of HER2 protein. Mechanistically, Melatonin treatment attenuated the protective effect of the HSP90 chaperone complex on its client protein HER2, triggering ubiquitylation and subsequent endocytic lysosomal degradation of HER2. The inhibitory effect of Melatonin on HER2 signaling substantially enhanced the cytotoxic effects of the pan-HER inhibitor Neratinib in HER2+ breast cancer cells. Lastly, we demonstrate that dual inhibition of HER2 by combined use of Melatonin and Neratinib effectively blocked the growth of HER2+ breast tumor xenografts in vivo. Our findings shed light on the potential use of Melatonin in a novel dual HER2 blockade strategy for HER2+ breast cancer treatment.

Abstract P3-10-26: Predicting benefit from HER2-targeted therapies in patients with ER+/HER2+ breast cancer

2019 ◽  
Author(s):  
AK Turnbull ◽  
V Webber ◽  
D McStay ◽  
L Arthur ◽  
C Martinez-Perez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapies ◽  
Her2 Breast Cancer
Sign in / Sign up

Export Citation Format

Share Document