Expert opinion

Episode 1: The use of biomarkers to inform and individualise treatment decisions for patients with early breast cancer

Dr Nadia Harbeck and Professor Alessandra Gennari discuss ground-breaking trials, including the TailorX and RxPonder trials, that validated the use of gene expression assays to inform therapy decisions for patients with early breast cancer. Dr Harbeck also describes the ADAPT series, which combines gene expression assays with endocrine response to individualise therapy.

Episode 2: The RxPonder trial – identifying patients most likely to benefit from adjuvant therapy

Dr Nadia Harbeck and Professor Alessandra Gennari delve deeper into the RxPonder trial to explore the design and primary outcomes of the trial. Dr Harbeck and Professor Gennari discuss how RxPonder validated the use of the 21-gene expression assay as a tool to identify patients who could be spared chemotherapy.

Episode 3: Explanations for the divergent results of PALLAS/PENELOPE-B and monarchE trials

Dr Nadia Harbeck and Professor Alessandra Gennari review the completed clinical trials for CDK4/6 inhibitors in early breast cancer, namely PALLAS and PENELOPE-B for palbociclib and monarchE for abemaciclib. The divergent results for palbociclib and abemaciclib were unexpected, particularly as both proved effective in the metastatic setting and are now standard therapy for this indication. Dr Harbeck and Professor Gennari share their views on the possible reasons for the different outcomes with palbociclib and abemaciclib in early breast cancer.

Episode 4: CDK4/6 inhibitors in the early breast cancer setting: Is the evidence clear? 

Dr Nadia Harbeck and Professor Michael Gnant review the latest clinical trial evidence for CDK4/6 inhibitors in the early breast cancer setting and discuss what the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) approval of abemaciclib means for clinicians and people with early breast cancer.

Episode 5: The many definitions for ‘high risk of recurrence’ in early breast cancer: What should inform clinical practice?

Recurrence risk is an important factor that must be considered in the treatment of early breast cancer. Dr Nadia Harbeck and Professor Michael Gnant discuss how recurrence risk and other factors can inform treatment selection.

Episode 6: The rapidly evolving treatment landscape for high-risk early breast cancer: Choosing the optimal treatment option

How might the early breast cancer treatment landscape change over the next 2 years? Dr Nadia Harbeck and Professor Michael Gnant review findings presented at ESMO 2023 and discuss approaches to optimal treatment selection in a rapidly evolving treatment landscape.

Meet the experts

Dr Nadia Harbeck

Dr Nadia Harbeck MD, PhD is head of the Breast Center and Chair of the Department of Obstetrics and Gynecology at LMU University Hospital in Munich, Germany. She is a member of the expert panel issuing the German AGO recommendations for breast cancer therapy, and Co-Director of the West German Study Group. From 2009 to 2015, Dr Harbeck served on the executive board of the European Organization for Research and Treatment of Cancer (EORTC) and was appointed subject editor for the ESMO Breast Cancer Guidelines in 2020. Professor Harbeck is principal investigator or steering committee member of numerous breast cancer trials, particularly with novel targeted compounds and individualized treatment strategies. She has a strong interest in eHealth and is a co-developer of CANKADO, an international digital patient diary (www.cankado.com).

Disclosures: Dr Harbeck has received honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, and Seagen for lectures and/or consulting.

Professor Alessandra Gennari

Professor Gennari MD, PhD is Head of Medical Oncology at the University of Eastern Piedmont in Novara, Italy. Her areas of expertise include diagnostic and therapeutic innovation in breast cancer. Her current research is focused on the identification of individual drug responsiveness in breast tumours and therapy optimisation in metastatic breast cancer. Other active research areas include the evaluation of host metabolism in breast cancer; functional imaging by PET-CT with ¹⁸F-fluoroestradiol to evaluate endocrine responsiveness in advanced breast cancer; and immunotherapy and response prediction in breast cancer. She is the principal investigator and coordinator of the ERA-NET JTC 2011 project (European TRANSCAN project) – Early prediction of efficacy of endocrine therapy in breast cancer: pilot study and validation with ¹⁸F-fluoroestradiol (ET-FES project).

Disclosures: Professor Genari holds consultancy, advisory roles, and speaker bureau involvement for AstraZeneca, Daiichi Sankyo, Eisai, Gentili, Gilead, Lilly, MSD, Novartis, Organon, Pfizer, Roche, and Seagen. She has also received non-profit research support from AIRC, the Italian Association for Cancer Research, EraNET Transcan, the Italian Ministry of Health, LILT Novara, MIUR Department of Excellence, and the University of Piemonte Orientale. Professor Gennari is a member of the scientific board for the International Breast Cancer Study Group (IBCSG) and has membership or affiliation with the Italian League for the Fight against Tumors (LILT) and the Fondazione Umberto Veronesi (FUV).

Professor Michael Gnant

Dr Michael Gnant, MD FACS FEBS, is Full Professor of Surgery at the Medical University of Vienna, Austria, where he also serves as President of the Austrian Breast & Colorectal Cancer Study Group. He has co-chaired and hosted the renowned St Gallen International Consensus Panel for Early Breast Cancer in Vienna since 2015. Dr Gnant’s research interests include several fields of surgical oncology, particularly breast and pancreatic cancer, immunotherapy, bone-targeted treatment for tumour micrometastases, tumour dormancy/quiescence and late relapse, pathway-directed therapies such as mTOR and CDK4/6 inhibition, and selective estrogen receptor degraders (SERDs). He has been the principal investigator of many (N>30) clinical trials in these fields.

Disclosures: Professor Gnant holds advisory roles with Daiichi Sankyo, Lilly, and Menarini–Stemline. Professor Gnant has also been a speaker for AstraZeneca, MSD, Novartis, Pierre Fabre, and Veracyte. While Professor Gnant has no financial ties to the following organisations, he has disclosed association with Pfizer as a trial chair and to Sandoz through his spouse.

The webinar ‘CDK4/6 inhibitors as adjuvant therapy for early breast cancer’ presented three pertinent topics related to the FDA and EMA approval for abemaciclib in managing HR+/HER2- early breast cancer at high risk of recurrence:

Session 1: Strategies for determining the risk of recurrence in early breast cancer 

• Speaker: Professor Joyce O’ Shoughnessy

Session 2: Emerging adjuvant treatments for early breast cancer

• Speaker: Dr Sara Tolaney

Session 3: Integrating CDK4/6 inhibitors into clinical practice for early breast cancer

• Speaker: Dr Gregory Vidal

Session 4: Q&A and panel discussion

• Speakers: Dr Gregory Vidal, Professor Joyce O’ Shoughnessy, Dr Sara Tolaney
  
  

Learn more about CDK4/6 inhibitors for early breast cancer management

Meet the Experts

Dr Gregory Vidal (West Cancer Center and Research Institute, University of Tennessee Health Science Center, USA)

Gregory Vidal MD, PhD, is a Medical Oncologist at West Cancer Center, Memphis Tennessee and Associate Professor at the University of Tennessee Health Science Center. Throughout his career Dr Gregory Vidal has had a keen interest in breast cancer research and treatment. His PhD thesis has contributed to the understanding of how the EGFR/H ER family of proteins influences breast cancer cells. While at Stanford University, his research focused on bridging the gap between the laboratory and the clinic in order to develop safe and effective treatments for breast cancer. He has been trained by world leading clinicians and researchers in the field of breast cancer. He now brings this expertise to West Cancer Center with the hopes of establishing a national and regional centre of excellence in the treatment and research of breast cancer.

Disclosures
Consulting fees: Roche/Genetech, Novartis, Eli Lilly, Gilead, Puma, Pfizer, AstraZeneca, Biotheranautics, Daiichi Sankyo, Concerto AI. Fees for non-CME services: Eli Lilly. Contracted research: Roche/Genetech, Puma, Celcuity, Merck, BMS, Eli Lilly, Astrazeneca, Pfizer, Gilead, GSK. Ownership: Oncodisc.

Dr Sara Tolaney (Division of Breast Oncology, Dana Faber Cancer Center, Boston, USA)

Sara Tolaney, MD, MPH, is the Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, and is internationally recognised for her research and education leadership in breast cancer. She serves as Associate Director of the Susan F Smith Center for Women’s Cancers, and is a Senior Physician at Dana-Farber Cancer Institute, and Associate Professor of Medicine at Harvard Medical School.

Dr Tolaney received her undergraduate degree from Princeton University, and her medical degree from UC San Francisco. She subsequently completed her residency in Internal Medicine at Johns Hopkins University, and fellowships in haematology and medical oncology at Dana-Farber Cancer Institute. She obtained her Masters in Public Health from Harvard School of Public Health.

Her research focuses on the development of novel therapies in the treatment of breast cancer and developing more effective and less toxic treatment approaches. Her work has demonstrated that a relatively low risk regimen is beneficial in women with early stage node-negative HER2+ cancers, and this work has been incorporated into national and international guidelines. She has developed several follow-up studies looking at novel approaches to early stage HER2+ disease, and has played a significant role in development of CDK 4/6 inhibitors, antibody drug conjugates, and immunotherapy in breast cancer. She currently chairs several registration studies in these areas, and leads many investigator-initiated trials. She is the author of over 150 peer-reviewed publications with manuscripts included in many prestigious journals such as the New England Journal, Lancet Oncology, Journal of Clinical Oncology, and JAMA Oncology.

Disclosures

Consulting or Advisory Role: Novartis, Pfizer, Merck, Lilly, Nektar, NanoString Technologies, AstraZeneca, Puma Biotechnology, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, Odonate Therapeutics, OncoPep, Kyowa Hakko Kirin, Samsung Bioepis, CytomX Therapeutics, Daiichi Sankyo, Athenex, Gilead, Mersana, Certara, Chugai Pharma, Ellipses Pharma, Infinity, 4D Pharma, OncoSec Medical Inc., BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics.

Research Funding: Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Eisai, AstraZeneca, NanoString Technologies, Cyclacel, Nektar, Gilead, Odonate Therapeutics, Sanofi, Seattle Genetics.

Professor Joyce O’Shoughnessy (Baylor-Sammons Cancer Center, Baylor University Medical Center, Texas Oncology and US Oncology, Dallas, USA)

Joyce A O’Shaughnessy, MD, specialises in medical oncology with board certification in internal medicine and medical oncology. She is a Diplomate of the American Board of Internal Medicine with subspecialty certification in medical oncology. Dr O’ Shaughnessy focuses on her practice and clinical research on breast cancer treatment. She is Director of Breast Cancer Research, and at Baylor-Sammons Cancer Center, and Chair of Breast Cancer Research for US Oncology.

Disclosures

Financial interest/relationship or affiliation in the form of: Consultant and/or Advisor for AbbVie Inc.; Agendia; Amgen Inc.; Aptitude Health; AstraZeneca; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd.; G1 Therapeutics, Inc.; Genentech, Inc.; Gilead Sciences, Inc.; GRAIL, Inc.; Halozyme, Inc.; Heron Therapeutics, Inc.; Immunomedics, Inc.; Ipsen Biopharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Myriad Genetics, Inc.; Novartis Pharmaceuticals Corporation; Ontada LLC; Pfizer; Pharmacyclics LLC; Pierre Fabre; Puma Biotechnology, Inc.; Prime Oncology; Samsung Bioepis; Sanofi; Seagen Inc.; Synthon International Holding B.V.

Introduction

In this webinar our experts, Dr Gregory Vidal, Professor Nadia Harbeck and Professor Stephen Johnston, will discuss the latest updates on managing the risk of recurrence in early breast cancer. Dr Vidal will cover the evolving treatment landscape in early breast cancer, Professor Harbeck will discuss the risk stratification tools available for therapy optimisation and Professor Johnston the emerging new evidence for new strategies in treating high-risk early breast cancer. 

Session 1 - Evolving Treatment Landscape in Early Breast Cancer 

In this talk, Dr Vidal covers the evolving treatment landscape in early breast cancer. He presents data on disease-free, event-free, and overall survival in breast cancer patients, touches upon checkpoint inhibitors and discussed the latest trials on survival rates following adjuvant chemotherapy and de-escalation therapy. 

Session 2 - Risk Stratification Tools in Early Breast Cancer for Therapy Optimisation

In this presentation, Professor Harbeck covers risk stratification tools in early breast cancer for therapy optimisation. She discusses the various factors associated with risk assessment in early breast cancer and goes into more detail on the information required for clinical decision making.

Session 3 - Emerging Evidence for New Strategies in Treating High-Risk Early Breast Cancer 

In this talk, Professor Johnston discussed the emerging evidence for new strategies in treating high-risk early breast cancer. He gives an overview of the currently approved CDK4/6 inhibitors and the trials of each, and then goes on to compare the PALLAS, monarchE and PENELOPE-B trials in detail. 

Q&A session  

Listen to this session to find out more about how to deal with the toxicity profiles of CDK4/6 inhibitors currently used and any problems that may arise with integrating these into treatments. More so, the implications of ESR1 mutations are discussed in early breast cancer and the trials currently running to address endocrine resistance due to these mutations.

Feedback survey   

In the HR+/HER2- metastatic breast cancer setting, healthcare professionals have moved away from first-line chemotherapy towards CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) as the new standard of care. This roundtable discussion event, led by experts Dr Gregory Vidal, Dr Laura Spring, Professor Nadia Harbeck and Dr Veronique Dieras, covers a series of topics related to management of metastatic breast cancer patients treated with CDK4/6 inhibitors in the clinic. It also provides an in-depth look into what the future holds for treatment of early breast cancer using CDK4/6 inhibitors.

Key topics include:

1. Roundtable introduction
2. Overview of the three CDK4/6 inhibitors in breast cancer
3. CDK4/6 inhibitor side effects and treatment monitoring in breast cancer
4. Side effect management, dose modification and switching treatments for CDK4/6 inhibitors in breast cancer
5. The future: considerations for managing early breast cancer in patients with CDK4/6 inhibitors – how will this be different?
6. Summary

Introduction

Expert speakers Dr Gregory Vidal, Dr Laura Spring, Professor Nadia Harbeck and Dr Veronique Dieras introduce themselves and the discussion topics. Topics include clinical data available in both advanced and curative breast cancer settings and optimal management of patients treated with CDK4/6 inhibitors.

Overview of the three CDK4/6 inhibitors in breast cancer

An overview of current clinical trials, treatment response and survival data provide insight into what the future holds for CDK4/6 inhibitors in the advanced setting, and how this might differ in high burden, HER2+ and triple negative breast cancer.

CDK4/6 inhibitor side effects and treatment monitoring in breast cancer

Clinical data on adverse event and tolerability profiles of CDK4/6 inhibitors for treatment of advanced breast cancer inform treatment choice and monitoring requirements of each inhibitor, which has also become increasingly important during the COVID-19 era. Could technology and development of mobile apps improve monitoring and management of symptoms and subsequent adherence to treatment?

Side effect management, dose modification and switching treatments for CDK4/6 inhibitors in breast cancer

Find out about label advice on managing side-effects of CDK4/6 inhibitors and case studies on how treatment and dose-modification strategies affect toxicity and efficacy. Additionally, what are the concerns about side effects of COVID-19 vaccinations in patients being treated with CDK4/6 inhibitors?

The future: considerations for managing early breast cancer in patients with CDK4/6 inhibitors – how will this be different? 

An in-depth discussion on current HR+/HER2- early breast cancer adjuvant phase III clinical trial results (monarchE, PALLAS, PENELOPE-B trials) and how these will impact treatment decisions for patients in the future. Gain insights into the differences in CDK4/6 inhibitor trial designs in the adjuvant setting and how tailored therapy can improve clinical outcome.

Summary

Our expert speakers Dr Gregory Vidal, Dr Laura Spring, Professor Nadia Harbeck and Dr Veronique Dieras conclude their thoughts on CDK4/6 inhibitors for breast cancer treatment.

Dr Gregory Vidal, MD, PhD

Dr Gregory Vidal, a medical oncologist at the West Cancer Center and Research Institute addresses some key questions on the use of CDK4/6 inhibitors for the treatment of HR+/HER2- metastatic breast cancer. Key discussion points include the safety and monitoring of abemaciclib, palbociclib and ribociclib in clinical practice and emerging investigational biomarkers of CDK4/6 resistance. He also discusses the importance of keeping up to date with the latest data for CDK4/6 inhibitors in treating breast cancer patients, as the field is ever-changing, with many new ongoing clinical trials in different patient settings.

Dr Gregory Vidal also helped to co-create an interactive eLearning module that further highlights the differences between the three CDK4/6 inhibitors; abemaciclib, palbociclib and ribociclib. The eLearning incorporates three patient cases for metastatic breast cancer, where one CDK4/6 inhibitor is better suited to each patient. The rationale for CDK4/6 inhibitor selection in each case is also discussed.

To go through the patient case studies, visit our eLearning module

Dr Laura Spring, MD

Dr Laura Spring from the Massachusetts General Hospital Cancer Center and Harvard Medical School tells us which factors influence her choice of CDK4/6 inhibitor for her patients. These include differences in both clinical and financial toxicity for the available inhibitors abemaciclib, palbociclib and ribociclib. She also highlights the need to understand resistance mechanisms, and cross-resistance between the three CDK4/6 inhibitors. Dr Spring also shares her excitement about the ongoing clinical trials for CDK4/6 inhibitors in the early breast cancer setting.

Dr Alistair Ring, MD, PhD

In this series of video clips, Dr Alistair Ring from The Royal Marsden in London talks about when he uses CDK4/6 inhibitors, both in general and in the context of endocrine resistant metastatic breast cancer. He also describes how he selects between the available CDK4/6 inhibitors, abemaciclib, palbociclib and ribociclib based on safety and patient comorbidities. He also points to the latest development in the utility of CDK4/6 inhibitors for metastatic breast cancer patients in the United Kingdom (UK).

Dr Gregory Vidal, MD, PhD

Dr Gregory Vidal, MD, PhD, is a Medical Oncologist at West Cancer Center and Research Institute and Assistant Professor at the University of Tennessee Health Science Center. Dr Vidal trained as a clinical researcher at the University of Stanford, taking part in research led by leading medical researchers. The aim of his research then, and now, is to discover and develop safe and effective treatments for breast cancer. Dr Vidal is the recipient of multiple awards and he has authored and co-authored numerous research articles in journals including the New England Journal of Medicine, Lancet Oncology and Nature Communications.

Dr Laura Spring, MD

Dr Laura Spring, MD, is a Medical Oncologist and clinical researcher at the Massachusetts General Hospital Cancer Center and Harvard Medical School. Dr Spring is particularly interested in targeted therapies in the neoadjuvant setting and has conducted multiple breast cancer research trials for localised metastatic breast cancer. She has authored and co-authored multiple research and review articles in journals including Lancet, The Lancet Oncology and Clinical Cancer Research. Dr Spring is also the recipient of the Young Investigator Award from the ASCO Conquer Cancer Foundation for her work on blood-based testing in the neoadjuvant setting using circulating tumour cell (CTC) monitoring.

Dr Alistair Ring, MD, PhD

Dr Alistair Ring, MD, PhD, is a Consultant Medical Oncologist at The Royal Marsden NHS Trust, and a principle investigator at the Institute of Cancer Research, London, UK. Dr Ring received his medical research degree at the Institute of Cancer in 2005 and his current research interests are in the management of early and metastatic breast cancer patients who are older. In 2018, he was appointed Honorary Reader in Breast Cancer Clinical Trials at the Institute of Cancer Research. He has authored and co-authored many peer-reviewed research articles in journals such as The Lancet Oncology, Cancer Research and the European Journal of Cancer.