Learning Objectives Introduction

Introduction

This educational touchFEATURE explores how treatment of patients with epidermal growth factor receptor positive non-small cell lung cancer (EGFR+ NSCLC) can be optimized.

Recognizing the role of EGFR in NSCLC, the potential impact of EGFR tyrosine kinase inhibitors (TKIs) and therefore the importance of identifying patients with EGFR mutations, are key to optimizing the management of this population. As new therapies for EGFR+ NSCLC emerge, it is important to understand both the differences and similarities, as these can inform treatment choices. Treatment resistance is extremely common, so it is also important to identify the underlying mechanism – such as the presence of a T790M mutation or mutations in other pathways – as this can be a key factor influencing the choice of subsequent EGFR TKIs.1 The availability of first-, second- and third-generation TKIs and the possibility of using these agents across therapeutic lines,2 offer valuable options for patients with EGFR+ NSCLC. However, the sequencing of these therapies is a key clinical consideration when optimizing outcomes for these patients.

The information in this activity is intended for oncologists, nurses and other healthcare professionals involved in the treatment of patients with lung cancer.

This touchFEATURE is an ACCME-accredited activity.

Learning objectives

After accessing our interactive touchFEATURE, you should be able to:

1 AMA PRA Category 1 Credits™ Date of original release: 03 May, 2019 Date credits expire: 03 May, 2020

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touchFEATURE

How do we optimize first-line treatment selection and sequencing for patients with EGFR+ NSCLC in the era of third-generation tyrosine kinase inhibitors?

1 AMA PRA Category 1 Credits™ Date of original release: 03 May, 2019 Date credits expire: 03 May, 2020

Clinical Spotlight

In Europe, approximately 15% of patients with NSCLC have EGFR+ disease.3 Treatment with EGFR TKIs has improved outcomes for this patient population, extending progression-free survival (PFS) from 5.6 months with chemotherapy to 11 months.4 This improvement highlights the importance of identifying patients with EGFR+ NSCLC. However, key clinical challenges remain: the inevitable development of resistance to EGFR TKIs,5,6 and treatment sequencing as the number of available agents increases.

Prof. Solange Peters provides an overview of the activity, which covers the importance of EGFR, the role played by EGFR TKIs, through to the evolution of treatment with successive agents. Emerging agents have started to address some of the challenges of treating patients with EGFR+ advanced NSCLC, such as the development of treatment resistance. However, how to sequence EGFR TKIs to maximize patient benefit remains a key clinical question.

 

Module 1: How can we use EGFR TKIs to optimize outcomes for patients with EGFR+ advanced NSCLC?

Professors Frank Griesinger, Solange Peters, David Planchard, Enriqueta Felip and Dr. Raffaele Califano consider the role of EGFR in NSCLC, how EGFR TKIs vary and the emergence of treatment resistance, as well as the use of biomarkers and treatment sequencing.

The constitutive activation of the EGFR signalling pathways leads to tumorigenesis. Several agents target EGFR to inhibit the signalling, and these have different efficacy and safety profiles that should be considered when making treatment choices. The EGFR TKIs improve outcomes for patients with EGFR+ disease, which illustrates the need to identify eligible patients.7 Overcoming the almost inevitable development of treatment resistance and optimizing treatment sequencing are ongoing clinical challenges.6,8,9 Improving outcomes after disease progression on third-generation EGFR TKI therapy and how this influences the sequence in which it is used is also an important consideration.

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Module 2: Patient journey: treat it right first time?

Professor Enriqueta Felip, Professor Frank Griesinger and Dr. Raffaele Califano present clinical cases addressing challenges in managing patients with EGFR+ advanced NSCLC.

Resistance mutations in patients with EGFR+ advanced NSCLC can emerge in response to treatment with EGFR TKIs and can influence the subsequent choice of therapy.10 The decision on how best to sequence EGFR TKIs in patients with EGFR+ NSCLC to maximize survival remains a key challenge.6,8,9 In addition, CNS metastases can develop and are challenging to treat. First- or second-generation EGFR TKIs show poor penetration into the CNS and patients may experience CNS relapse when treated with these agents.11 Early data support the ability of a third-generation EGFR TKI to cross the blood–brain barrier and penetrate the CNS, which may offer protection for the CNS, as well as treating metastases that are already present.6

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Module 3: Panel discussion – Third-generation EGFR TKIs: how can we use them now and in the future?

Professors Solange Peters, Enriqueta Felip and David Planchard discuss the role of third-generation EGFR TKIs in the first-line treatment of EGFR+ NSCLC and the implications of this choice on subsequent treatment outcomes.

The third-generation EGFR TKI has been found to be effective in patients with the commonly acquired T790M mutation and has demonstrated significant increases in progression-free survival over standard-of-care treatment as both first- and second-line therapy.8,9 This raises key questions on how best to use third-generation EGFR TKIs and how to optimize outcomes for patients with EGFR+ advanced NSCLC. The European Society of Medical Oncology (ESMO) clinical practice guidelines2 have recently been updated to incorporate the use of the third-generation EGFR TKI in the first-line setting, although it is not clear how this will impact clinical practice and treatment sequencing. This therapeutic landscape continues to evolve rapidly – what does the future hold for EGFR+ NSCLC treatment?

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Professor and Chair of Medical Oncology, University Hospital of Lausanne, Lausanne, Switzerland.

Professor Peters specializes in thoracic tumours, lung cancer and pleural tumours. Her main fields of interest are new biomarkers discovery and validation in preclinical and clinical settings, multimodality strategies for locally advanced NSCLC, as well as cancer immunotherapy. She acts as the local principal investigator (PI) for lung trials opened at Lausanne Cancer Centre, focused on phase I predictive biomarkers and thoracic malignancies immunotherapy, and is a co-PI of several other trials. Additionally, she acts as the scientific coordinator and Foundation Council member of the European Thoracic Oncology Platform. Professor Peters has authored numerous peer-reviewed manuscripts and book chapters, and serves as deputy editor of the Journal of Thoracic Oncology, and on the editorial board of several other oncology journals. Professor Peters is active in the educational programmes of the European Society for Medical Oncology (ESMO) and the International Association for the Study of Lung Cancer (IASLC), notably working as the current editor of the ESMO lung cancer clinical practice guidelines. She is the Chair of ESMO Women for Oncology Committee, and she is the youngest ESMO President-elect ever, with a mandate in 2020–2021. She was also a member of the IASLC board of directors, and acts as vice president of the Swiss Group for Clinical Cancer Research (lung division).

Disclosures: Professor Peters has received funding from Abbvie, Amgen, AstraZeneca, Bayer, Biocartis, Boehringer-Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics and Takeda.

Consultant Medical Oncologist at The Christie Hospital and Manchester University Hospital and Honorary Senior Lecturer in Cancer Sciences, The University of Manchester, Manchester, UK.

Dr Califano has a special interest in thoracic malignancies and clinical cancer research and is an active member of the Manchester Lung Cancer Group. He has been an investigator for several Phase 1b–3 clinical trials, developing a particular interest for molecularly-driven clinical trials in advanced NSCLC, small cell lung cancer and mesothelioma, and his research focus has been on immunotherapy and oncogenic-driven lung cancer. Dr Califano serves as Chairman of the ESMO Publishing Working Group and as a member of the Steering Committee of the ESMO Educational Committee. He is also a member of British Thoracic Oncology Group (BTOG) and the International Association for the Study of Lung Cancer (IASLC). Dr Califano is the author of several papers published in indexed peer-reviewed international journals and he has been an invited speaker to several national and international oncology meetings.

Disclosures: Dr Califano has received funding from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Lilly Oncology, Merck Sharp and Dohme, Novartis, Pfizer, Roche and Takeda. He has received research funding from Abbvie, AstraZeneca, Bristol Myers Squibb, Clovis, Lilly Oncology, Merck Sharp and Dohme, Novartis, Pfizer, Roche and Takeda.

Associate Professor of Medicine, Department of Medicine, Gustave Roussy, Villejuif, France.

Professor Planchard is the lead for clinical trials (mainly Phase 1 and 2) in thoracic diseases and has worked to build a long-term clinical research strategy based on molecular screening. Over the past 10 years, he has been a principal investigator and co-investigator for more than 100 Phase 1, 2 and 3 trials and has published in several international peer-reviewed journals. His current research interests include genomic analysis (and high-throughput technologies) to drive lung cancer patients into specific targeted agents. Professor Planchard is a member of AACR, ASCO and ESMO.

Disclosures: Professor Planchard has received funding from Abbvie, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, MedImmune, Novartis, Novocure, Pfizer, prIME Oncology, Roche, Sanofi-Aventis and Taiho Pharma.

Head of the Thoracic Cancer Unit, Oncology Department, Vall d’Hebron Hospital, Barcelona, Spain,

Professor Felip leads the thoracic malignancy service and thoracic cancer trials at Vall d’Hebron Hospital. She is a member of the Spanish Lung Cancer Group (SLCG), the Spanish Society of Medical Oncology (SEOM), ESMO, the American Society of Clinical Oncology (ASCO) and the IASLC. She has been involved in several initiatives with scientific organizations, including as Subject Editor of the Guidelines Working Group ESMO Minimum Clinical Recommendations in lung cancer, coordinator of the first ESMO Consensus Conference in lung cancer and coordinator of the European School of Oncology (ESO) lung cancer programme. Professor Felip has authored several peer-reviewed articles and book chapters relating to the field of thoracic malignancies.

Disclosures: Professor Felip has received funding from Abbvie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Guardant Health, Merck Sharp & Dohme, Novartis, Pfizer, Roche and Takeda.

Professor of Internal Medicine and Oncology at the University of Oldenburg, Oldenburg, Germany.

Professor Griesinger has a particular interest in the molecular understanding of malignant diseases, with a focus on lung cancer. He is currently the Deputy Speaker of the Steering Committee of the Thoracic Oncology Group of the AIO Germany, the representative of the German Society of Haematology and Oncology (DGHO) in the S3 Guideline Programme of the German Cancer Society and the lead author of the Oncopedia Recommendations of the DGHO for Lung Cancer. He is also a member of the IASLC educational committee and is involved in a number of lung cancer clinical trials. He coordinates the prospective registry CRISP in Germany and leads the NOWEL network in lung cancer. Professor Griesinger has published more than 100 peer-reviewed papers and is a member of ASCO, AIO, ASH, DGHO, DGIM and ESMO.

Disclosures: Professor Griesinger has received funding from Abbvie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Medac, Merck Sharp and Dohme, Novartis, Pfizer, Roche and Takeda.

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