Adjuvant abemaciclib plus endocrine therapy previously showed a significant improvement in invasive disease-free survival and distant relapse-free survival in hormone receptor-positive, human epidermal growth factor receptor 2 (HER2; also known as ERBB2)-negative, node-positive, high-risk, early breast cancer. Here, we report updated results from an interim analysis to assess overall survival as well as invasive disease-free survival and distant relapse-free survival with additional follow-up.In monarchE, an open-label, randomised, phase 3 trial, adult patients (aged ≥18 years) who had hormone receptor-positive, HER2-negative, node-positive, early breast cancer at a high risk of recurrence with an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 603 sites including hospitals and academic and community centres in 38 countries. Patients were randomly assigned (1:1) by means of an interactive web-based response system (block size of 4), stratified by previous chemotherapy, menopausal status, and region, to receive standard-of-care endocrine therapy of physician's choice for up to 10 years with or without abemaciclib 150 mg orally twice a day for 2 years (treatment period). All therapies were administered in an open-label manner without masking. High-risk disease was defined as either four or more positive axillary lymph nodes, or between one and three positive axillary lymph nodes and either grade 3 disease or tumour size of 5 cm or larger (cohort 1). A smaller group of patients were enrolled with between one and three positive axillary lymph nodes and Ki-67 of at least 20% as an additional risk feature (cohort 2). This was a prespecified overall survival interim analysis planned to occur 2 years after the primary outcome analysis for invasive disease-free survival. Efficacy was assessed in the intention-to-treat population. Safety was assessed in all treated patients. The study is registered with ClinicalTrials.gov, NCT03155997, and is ongoing.Between July 17, 2017, and Aug 12, 2019, 5637 patients were randomly assigned (5601 [99·4%] were women and 36 [0·6%] were men). 2808 were assigned to receive abemaciclib plus endocrine therapy and 2829 were assigned to receive endocrine therapy alone. At a median follow-up of 42 months (IQR 37-47), median invasive disease-free survival was not reached in either group and the invasive disease-free survival benefit previously reported was sustained: HR 0·664 (95% CI 0·578-0·762, nominal p<0·0001). At 4 years, the absolute difference in invasive disease-free survival between the groups was 6·4% (85·8% [95% CI 84·2-87·3] in the abemaciclib plus endocrine therapy group vs 79·4% [77·5-81·1] in the endocrine therapy alone group). 157 (5·6%) of 2808 patients in the abemaciclib plus endocrine therapy group died compared with 173 (6·1%) of 2829 patients in the endocrine therapy alone group (HR 0·929, 95% CI 0·748-1·153; p=0·50). The most common grade 3-4 adverse events were neutropenia (in 548 [19·6%] of 2791 patients receiving abemaciclib plus endocrine therapy vs 24 [0·9%] of 2800 patients in the endocrine therapy alone group), leukopenia (318 [11·4%] vs 11 [0·4%]), and diarrhoea (218 [7·8%] vs six [0·2%]). Serious adverse events occurred in 433 (15·5%) of 2791 patients receiving abemaciclib plus endocrine therapy versus 256 (9·1%) of 2800 receiving endocrine therapy. There were two treatment-related deaths in the abemaciclib plus endocrine therapy group (diarrhoea and pneumonitis) and none in the endocrine therapy alone group.Adjuvant abemaciclib reduces the risk of recurrence. The benefit is sustained beyond the completion of treatment with an absolute increase at 4 years, further supporting the use of abemaciclib in patients with high-risk hormone receptor-positive, HER2-negative early breast cancer. Further follow-up is needed to establish whether overall survival can be improved with abemaciclib plus endocrine therapy in these patients.Eli Lilly. 

Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial.

The CDK4/6 inhibitor revolution - a game-changing era for breast cancer treatment.

Novel systemic therapies for breast cancer are being rapidly implemented into clinical practice. These drugs often have different mechanisms of action and side-effect profiles compared with traditional chemotherapy. Underpinning practice-changing clinical trials focused on the systemic therapies under investigation, thus there are sparse data available on radiotherapy. Integration of these new systemic therapies with radiotherapy is therefore challenging. Given this rapid, transformative change in breast cancer multimodal management, the multidisciplinary community must unite to ensure optimal, safe, and equitable treatment for all patients. The aim of this collaborative group of radiation, clinical, and medical oncologists, basic and translational scientists, and patient advocates was to: scope, synthesise, and summarise the literature on integrating novel drugs with radiotherapy for breast cancer; produce consensus statements on drug-radiotherapy integration, where specific evidence is lacking; and make best-practice recommendations for recording of radiotherapy data and quality assurance for subsequent studies testing novel drugs. 

International multidisciplinary consensus on the integration of radiotherapy with new systemic treatments for breast cancer: European Society for Radiotherapy and Oncology (ESTRO)-endorsed recommendations.

Safety profile of cyclin-dependent kinase (CDK) 4/6 inhibitors with concurrent radiation therapy: A systematic review and meta-analysis.

Prevalence of survivors of breast cancer has been steadily increasing in the last 20 years. Currently, more than 90% of women diagnosed with early-stage breast cancer are expected to be alive at 5 years from diagnosis thanks to early detection and breakthrough innovations in multimodal treatment strategies. Alongside this advancement in clinical outcomes, survivors of breast cancer might experience several specific challenges and present with unique needs. Survivorship trajectories after diagnosis and treatment of breast cancer can be significantly impacted by long-lasting and severe treatment-related side effects, including physical problems, psychological distress, fertility issues in young women, and impaired social and work reintegration, which add up to patients’ individual risk of cancer recurrence and second primary malignancies. Alongside cancer-specific sequelae, survivors still present with general health needs, including management of chronic preexisting or ensuing conditions. Survivorship care should implement high-quality, evidence-based strategies to promptly screen, identify, and address survivors’ needs in a comprehensive way and minimize the impact of severe treatment sequelae, preexisting comorbidities, unhealthy lifestyles, and risk of recurrence on quality of life. This narrative review focuses on core areas of survivorship care and discuss the state of the art and future research perspectives in key domains including selected long-term side effects, surveillance for recurrences and second cancers, well-being promotion, and specific survivors’ needs. 

/pdf/the-future-of-breast-cancer-research-in-the-survivorship-2r340p90.pdf

The Future of Breast Cancer Research in the Survivorship Field

http://www.annalsofoncology.org/article/S0923753422003830/pdf

Adjuvant Abemaciclib Combined with Endocrine Therapy for High Risk Early Breast Cancer: Safety and Patient-Reported Outcomes From the monarchE Study.


 Introduction: HER2 is overexpressed on 15-20% of breast cancers and is a clinically important cancer driver. In spite of the HER2 targeted therapy’s success, most patients in the metastatic setting will eventually experience disease progression. ARX788 is an antibody drug conjugate (ADC) that consists of an anti-HER2 mAb and a potent tubulin inhibitor payload AS269, that is site-specifically conjugated to the antibody via a non-natural amino acid incorporated into antibody by using a proprietary EuCODE technology platform. The phase 1 study ACE-Breast-01 (ZMC-ARX788-111 [CTR20171162]) evaluates the safety, pharmacokinetics, and efficacy of ARX788 in patients in China with metastatic HER2-positive breast cancer. Methods: ACE-Breast-01 is an open label, single site, dose escalation study using a 3+3 study design in 69 heavily pretreated patients (median of 6 prior lines of therapy, range: 2-17) with metastatic HER2-positive breast cancer who received intravenous ARX788. While the ARX788 MTD has not been determined, the 1.5 mg/kg of ARX788 dose is reported herein. Eligible patients had histologically documented, incurable, locally advanced or metastatic HER2+ (IHC 3+ and/or FISH positive) breast cancer whose disease had failed prior anti-HER2 treatments in the advanced disease setting; ECOG performance ≤1; adequate organ function; no history of interstitial lung disease or other significant lung disease; no radiotherapy for pulmonary diseases including lung parenchyma; no history of keratitis, corneal disease, or active ocular infection; no unstable brain or spinal cord metastasis; and no history of hypersensitivity to trastuzumab or any component of ARX788. The DLT assessment period was 84 days for pulmonary toxicity and one cycle of duration for all other toxicities. Investigators assessed efficacy using RECIST 1.1 and evaluated safety using NCI-CTCAE V.4.1. Results: Nineteen patients showed clinical response in the 1.5 mg/kg Q3W cohort, with the confirmed objective response rate of 66% (19/29, exact 95% CI, 45.7% to 82.1%), with median duration of response of 14.4 months [95% CI (9.0, NA)]. The disease control rate (CR + PR + SD) among the 29 patients treated was 100%. All patients (29/29, 100%) received prior trastuzumab in addition to other anti-HER2 treatments. Patients were heavily treated with prior HER2-targeted therapies and demonstrated robust ORR ranging from 65-80% (Table 1). ARX788 was generally well tolerated with most adverse events being grade 1 or 2 and were manageable. Low systemic toxicity (low incidence and low grade of neutropenia, thrombocytopenia, anemia, decrease WBC counts, nausea, vomiting, constipation, fatigue, etc.) was observed. No DLT or drug-related deaths occurred, as of data cut-off of 30-Jun-2021. Conclusion: At the 1.5 mg/kg dose level, ARX788 had robust anti-tumor activity in patients whose disease was resistant/refractory to other HER2 targeted therapies and was generally well tolerated with low systemic toxicity.
 Table 1.Summary of ACE-Breast-01 Confirmed ORR in patients whose disease is resistant or refractory to prior HER2 treatment (trastuzumab, ADCs, TKIs, and bispecific antibodies) at ARX788 1.5 mg/kg Q3WPrior anti-HER2 therapy*Confirmed ORRTrastuzumab containing regimens*19/29 (66%)HER2 ADCs (T-DM1, DX126-262, A166, BAT8001, and HS630) regimens**4/5 (80%)​HER2 TKIs (lapatinib, pyrotinib, neratinib, AST-1306, and Hemay-022) regimens15/23 (65%)​Both HER2 ADC and HER2 TKI regimens3/4 (75%)Bispecific antibodies (KN026 and M802) containing regimens3/4 (75%)*All patients (29/29) received prior trastuzumab-containing regimens.**One patient who received prior pertuzumab also achieved confirmed PR.
 Citation Format: Jiang Zhang, Dongmei Ji, Weina Shen, Qin Xiao, Yajia Gu, Joyce O’Shaughnessy, Gang Xia, Yanping Ji, Gaozhun Xiong, Matt Li, Dong Xu, Robert Cartmell, Cynthia Song, Jinchun Yan, Xichun Hu. Safety and anti-tumor activity of ARX788 in HER2-positive metastatic breast cancer patients whose disease is resistant/refractory to HER2 targeted agents (trastuzumab, ADCs, TKIs, and bispecific antibodies): ACE-Breast-01 trial results [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD8-04.

Abstract PD8-04: Safety and anti-tumor activity of ARX788 in HER2-positive metastatic breast cancer patients whose disease is resistant/refractory to HER2 targeted agents (trastuzumab, ADCs, TKIs, and bispecific antibodies): ACE-Breast-01 trial results


 Background: The HER2 receptor is a cancer driver which is overexpressed on 15-20% of breast cancers. Though historically survival is poor with this disease subtype, HER2+ targeted therapy has improved survival in both early and advanced disease. In spite of this, most patients in the metastatic setting will eventually experience disease progression and death. Therefore, new therapeutic options and innovative treatments are needed for patients with recurrent or refractory disease. ARX788 is a next-generation antibody–drug conjugates (ADC) using a technology platform whereby a HER2 specific monoclonal antibody is conjugated with Amberstatin269, a potent cytotoxic tubulin inhibitor. Site-specific, high homogenous, and stable covalent conjugation in ARX788 leads to slow release and prolonged peak of serum pAF-AS269, which may contribute to the lower systemic toxicity, increased targeted delivery of payload to tumor cells, and lower effective dose compared to other HER2 ADCs.Methods: ACE-Breast-03 (NCT04829604) is a global, single arm, phase 2 study designed to assess anticancer activity and safety of ARX788 in patients with metastatic HER2 positive breast cancer. Patients whose disease is resistant or refractory to T-DM1, and/or T-DXd, and/or tucatinib-containing regimens are eligible. Patients must have adequate organ function and any brain metastasis must demonstrate radiographic stability and lack of steroid dependence. Approximately 200 subjects with advanced HER2-positive breast cancer will be enrolled. ARX788 will be administered as an intravenous (IV) infusion at 1.5 mg/kg as the initial dose on Day 1 of the first 4-week cycle and followed by 1.3 mg/kg at every subsequent 4-week cycle. Efficacy will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 via imaging every 8 weeks (±7 days) on study and endpoints include objective response rate (ORR), duration of response (DOR), time to response (TTR), best overall response (BOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The safety and tolerability profile will be assessed. Blood samples will be collected at specified time points to determine serum concentrations of ARX788 (intact ADC), total antibody, and metabolite pAF-AS269. Biomarkers (e.g., cell-free DNA, serum HER2 extracellular domain, and circulating tumor cells) at baseline and on-treatment will be analyzed for exploratory research. Descriptive statistics will be used to evaluate anticancer activity, safety, and tolerability. The study is currently recruiting patients. Please contact breast03trialinquiry@ambrx.com for additional information.
 Citation Format: Janice Lu, Kevin M Kalinsky, Debu Tripathy, George W Sledge, William Gradishar, Ruth O’Regan, Joyce O’Shaughnessy, Shanu Modi, Joshua Drago, Haeseong Park, Amelia McCartney, Sophia Frentzas, Catherine Shannon, Katharine Cuff, Richard Eek, Miguel Idzwan Martin, Giuseppe Curigliano, Guy Jerusalem, Chiun-Sheng Huang, Michael Press, Matt Li, Dong Xu, Cynthia Song, Richard Huhn, Jinchun Yan, Sara Hurvitz. A global, phase 2 study of ARX788 in patients with HER2-positive metastatic breast cancer whose disease is resistant or refractory to T-DM1, and/or T-DXd, and/or tucatinib-containing regimens [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-02-02.

Abstract OT1-02-02: A global, phase 2 study of ARX788 in patients with HER2-positive metastatic breast cancer whose disease is resistant or refractory to T-DM1, and/or T-DXd, and/or tucatinib-containing regimens

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

C. Song

Author Tools

Chat about Author

Papers

Adjuvant Abemaciclib Combined with Endocrine Therapy for High Risk Early Breast Cancer: Safety and Patient-Reported Outcomes From the monarchE Study.

Abstract PD8-04: Safety and anti-tumor activity of ARX788 in HER2-positive metastatic breast cancer patients whose disease is resistant/refractory to HER2 targeted agents (trastuzumab, ADCs, TKIs, and bispecific antibodies): ACE-Breast-01 trial results

Abstract OT1-02-02: A global, phase 2 study of ARX788 in patients with HER2-positive metastatic breast cancer whose disease is resistant or refractory to T-DM1, and/or T-DXd, and/or tucatinib-containing regimens