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Targeting the PI3K/AKT pathway in HR+ HER2- advanced breast cancer

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Breast Cancer Watch Time: 32 mins

touchEXPERT OPINIONS Targeting the PI3K/AKT pathway in HR+ HER2- advanced breast cancer

Watch leading experts discuss new and emerging agents targeting the PI3K/AKT pathway in HR+ HER2- breast cancer, including how to manage key side effects.

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Prof. Fabrice André
Director of Research, Institut Gustave Roussy, Villejuif, France
Targeting the PI3K/AKT pathway in HR+ HER2- advanced breast cancer: Rationale and drug development

Prof. Fabrice André discusses the rationale for targeting the PI3K/AKT signalling pathway in breast cancer and describes the development of approved and emerging PI3K and AKT inhibitors for HR+ HER2- advanced breast cancer.

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Interview Questions

In this interview, Prof. Fabrice André answers the following questions:

  • What is the role of the PI3K/AKT pathway in HR+ advanced breast cancer?
  • Why is selective inhibition of the alpha isoform of PI3K an attractive strategy in endocrine-resistant breast cancer?
  • Taselisib is an inhibitor specific to PIK3CA that was investigated in the SANDPIPER trial. Why was regulatory submission not pursued for this agent?
  • What is the evidence for the efficacy of the approved agent, alpelisib, for the treatment of endocrine-resistant HR+ HER2- advanced breast cancer?
  • What other inhibitors targeting the PI3K/AKT pathway are currently in clinical development?
About Prof. Fabrice André

Fabrice André, MD, PhD, is Head of Research and Professor in the Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. He received his MD in Grenoble in 2002, and a PhD in Biotechnology from Paris University in 2005. read more

His research work in the field of biomarkers and personalized therapies focuses on biomarker discovery, development of targeted agents and implementation of personalized medicine. He is also leading phase I–III trials testing targeted agents in the field of breast cancer and large national trials testing implementation of high-throughput technologies in the healthcare system.

Prof. André is president of the Unicancer (French cooperative group) Personalized Medicine Group and has been Editor-in-Chief of Annals of Oncology since September 2017. He has been a member of the ESMO Educational Committee since 2009 and the ESMO Breast Cancer Faculty since 2015. He is also currently chair of the ESMO Translational Research and Precision Medicine Working Group.

Prof. Fabrice André discloses: Institutional financial interests and research grant from AstraZeneca, Daiichi, Eli Lilly, Novartis, Pfizer, Roche. 

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Dr Judy King
Consultant Medical Oncologist, Royal Free London NHS Foundation Trust, London, UK
PI3K/AKT inhibitors: What are the key adverse events?

Dr Judy King describes the key safety data from clinical trials of approved and investigational PI3K and AKT inhibitors for HR+ HER2- advanced breast cancer.

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Interview Questions

In this interview, Dr Judy King answers the following questions:

  • What do the adverse event data from the SOLAR-1 trial tell us about the safety profile of alpelisib?
  • Were any new safety concerns reported with alpelisib in the BYLieve trial?
  • Preliminary safety data have been reported for the investigational PI3KCA inhibitor, GDC-0077. What were the key AEs observed with this agent?
  • What was the pattern of AEs reported with the AKT inhibitor, capivasertib, in the phase II FAKTION trial?
About Dr Judy King

Dr Judy King is a Consultant Medical Oncologist at the Royal Free London NHS Foundation Trust in the UK. She qualified from Cambridge University and Guy’s and St Thomas’ School of Medicine and Dentistry in 2001 and completed a PhD in T-cell immunotherapy of malignancies in 2008. During her specialty training, she also completed a Darzi Fellowship in Leadership and Management and completed a Postgraduate Certificate from Leeds Business School. read more

Dr King’s main research interest is in combining chemotherapy and novel agents with immunotherapy and HER2-directed therapies. She also sits on the Joint Specialty Committee for Medical Oncology at the Royal College of Physicians and is Oncology Training Director for the Royal Free Hospital.

Dr Judy King discloses: Advisory board/consultancy fees from Eisai, Eli Lilly and Company, Genomic Health, Novartis, Pfizer Inc. and Roche. 

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Dr Eva M Ciruelos
Medical Oncologist and Coordinator, Breast Cancer Unit, University Hospital 12 de Octubre and HM Hospitales, Madrid, Spain
Integrating PI3K/AKT pathway-targeted agents into practice: How to manage the side effects

Dr Eva M Ciruelos discusses the practical management of important side effects associated with PI3K/AKT inhibitor therapy, namely hyperglycaemia, rash and diarrhoea.

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Interview Questions

In this interview, Dr Eva M Ciruelos answers the following questions:

  • What are the key side effects associated with drugs targeting the PI3K/AKT pathway and why is it important to manage them promptly?
  • What causes hyperglycaemia during PI3K/AKT pathway inhibition and how is it optimally managed?
  • How should skin toxicities, such as rash, be treated and what is the evidence for early intervention?
  • What are the key measures for managing diarrhoea in patients taking a PI3K/AKT inhibitor?
  • Why is a multidisciplinary approach important to facilitate effective management of the side effects of PI3K/AKT inhibitors in clinical practice?
About Dr Eva M Ciruelos

Dr Eva M Ciruelos is Medical Oncologist and Coordinator of the Multidisciplinary Breast Cancer Unit at the University Hospital 12 de Octubre in Madrid, Spain; current coordinator of the Breast Cancer Unit at HM private hospitals in Madrid; and an Associate Professor in the Department of Medicine at the Complutense University of Madrid Faculty of Medicine. read more

Dr Ciruelos received her medical degree from the Autonoma University of Madrid in 1996 and completed her training in Medical Oncology at the University Hospital 12 de Octubre in 2001. 

Dr Ciruelos is the Principal Investigator of several clinical trials and research projects in breast cancer. She is the current Vice President of the Solid Tumor Intensification (SOLTI) Group, is a member of the Scientific Committee of the Breast International Group (BIG) and has been a member of the St Gallen Conference Panel since 2017.

Dr Ciruelos is author and reviewer of national and international oncology practice guidelines and numerous articles with a focus on breast cancer research and plays an active role in breast cancer medical education events.

Dr Eva M Ciruelos discloses: Personal fees for speaker and advisory board services from Eli Lilly, Novartis. Personal fees for speaker and advisory board services and congress assistance from Pfizer, Roche.

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Overview & Learning Objectives
Overview

Watch leading experts discuss new and emerging agents targeting the PI3K/AKT pathway in HR+ HER2- breast cancer, including how to manage key side effects.

Learning Objectives

After watching this activity, you should be better able to:

  • Recall the rationale for targeting the PI3K/AKT pathway in HR+ HER2- breast cancer and approved/investigational agents that target this pathway
  • Review the safety data for approved and emerging drugs targeting the PI3K/AKT pathway in HR+ HER2- breast cancer
  • Discuss the management of key side effects associated with drugs targeting the PI3K/AKT pathway

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