Targeted therapies in lung cancer : management strategies for nurses and practitioners

This book aims to educate nurses and advanced practice providers (APP’s) about known mutations, availability of targeted therapy and the management of patients with non-small cell lung cancer (NSCLC). It will educate nurses and practitioners about the scope of therapy to assure safe and effective lung cancer treatment. In this era of personalized medicine, nurses and APP’s are responsible for guiding patients from diagnosis through treatment. This starts with the identification of patients that can benefit from these therapies, the key role of biopsy acquisition (ie. what to test, when and how often) and treatment selection based on the mutation identified. Readers will learn about the mechanisms of action, administration, potential adverse side effects and unique management strategies for these targeted agents. Lung cancer continues to be the leading cause of cancer death in the United States and worldwide. Recent advances in the identification of specific oncogenic mutations that drive cancer development, growth and metastasis have led to major paradigm shifts in lung cancer treatment. Sophisticated methods are required to identify specific mutations at the time of diagnosis. This book explains how molecularly targeted therapies have been developed that target these drivers. To date, several tyrosine kinase inhibitors have been approved to target the epidermal growth factor receptor (EGFR), EML4-ALK ,ROS1 and BRAF. Most recently, immune checkpoint inhibitors have been approved with some indication that efficacy may be enhanced for patients who overexpress PD-L1. While some driver mutations have been identified, there is ongoing investigation into additional mutations. In the case of driver mutations, lung cancers will develop resistance to therapy. This book provides nurses and APP’s with the mechanisms of resistance that have been identified such as T790 mutation and many others in the EGFR mutation, and shows how the next level of drug development is focused on identifying mechanisms of resistance and development of new agents that overcome these mutations. With this book in hand, nurses and practitioners will be able to navigate patients through this ever expanding field of lung cancer treatment. Contents 1: Introduction References 2: Introduction to Mutation Testing 2.1 Introduction/Lung Cancer Statistics/Histology 2.2 Types of Lung Cancer Mutations 2.2.1 EGFR 2.2.2 ALK 2.2.3 ROS1 2.2.4 BRAF 2.2.5 KRAS 2.2.6 ERBB2 (HER2) 2.2.7 MET 2.2.8 NTRK 2.2.9 Other 2.3 Mechanism of Resistant Mutations 2.4 Patient Selection for Molecular Testing 2.5 Role of Nursing and Advanced Practice Providers (APP) and Team Approach to Molecular Testing References 3: Nursing Considerations with EGFR Inhibitors in NSCLC 3.1 The Epidermal Growth Factor Receptor Mutation 3.1.1 The EGFR Inhibitors 3.2 Toxicities of EGFR Inhibitors References 4: Nursing Considerations with ALK and ROS1 Inhibitors in NSCLC 4.1 Introduction 4.2 ALK Positive NSCLC 4.2.1 Crizotinib 4.2.2 Ceritinib 4.2.3 Alectinib 4.2.4 Brigatinib 4.2.5 Lorlatinib 4.3 ROS1 Positive NSCLC 4.3.1 Crizotinib 4.3.2 Other Treatments 4.4 Toxicities and Management of ALK/ROS1 Inhibitors 4.4.1 Pneumonitis 4.4.2 Fatigue 4.4.3 Visual Disturbances 4.4.4 GI Toxicities 4.4.5 Cardiovascular Toxicities 4.4.6 Laboratory Abnormalities 4.4.7 Other 4.5 Conclusions References 5: BRAF in NSCLC 5.1 Overview and Mechanism of Action of BRAF Mutations in NSCLC 5.2 Data for BRAF 5.3 Toxicities and Management 5.3.1 Previously Treated Patients 5.3.2 Melanoma Patients 5.3.3 Pyrexia 5.3.4 Cutaneous Skin Reactions 5.3.5 Hypertension 5.3.6 LVEF 5.3.7 QTc Prolongation 5.3.8 Ocular Toxicities 5.4 Conclusion References 6: Mechanisms of Acquired Resistance to Targeted Therapy in NSCLC: Role of Repeat Biopsy and Nursing Considerations 6.1 Background 6.2 Utility of Repeat Biopsy: Tissue Testing 6.3 Utility of Repeat Biopsy: Liquid Biopsy 6.4 Mechanisms of Acquired Resistance 6.4.1 EGFR Acquired Resistance Mutations 6.4.1.1 Primary Resistance 6.4.1.2 Acquired Resistance 6.4.1.3 Secondary Resistance 6.4.1.4 Tertiary Resistance 6.4.2 ALK Acquired Resistance Mutations 6.5 Summary References 7: The Impact and Toxicity of Checkpoint Inhibitors in Management of Lung Cancer 7.1 Introduction 7.1.1 Immune Checkpoint Inhibitor Agents 7.2 Mechanism of Action 7.3 Patient Selection 7.4 Results of Clinical Trials 7.4.1 Metastatic Disease: First-Line Therapy 7.4.1.1 Pembrolizumab Monotherapy 7.4.1.2 Pembrolizumab Plus Chemotherapy 7.4.1.3 Atezolizumab Plus Chemotherapy 7.4.2 Metastatic Disease: Second-Line Monotherapy 7.4.2.1 Combination Checkpoint Inhibitors 7.4.2.2 Combinations with Radiation 7.4.2.3 Consolidation Therapy 7.4.2.4 Small Cell Lung Cancer 7.4.2.5 Mesothelioma: Second and Third Line 7.5 Management of Immune-Related Adverse Events 7.5.1 Management of Select irAEs 7.5.1.1 Pneumonitis 7.5.1.2 Colitis 7.5.1.3 Dermatitis 7.5.1.4 Hepatitis 7.5.1.5 Endocrinopathies 7.6 Patient Education 7.7 Supportive Care 7.8 Future Developments References 8: The Role of Anti-Angiogenic Agents (VEGF) 8.1 Angiogenesis 8.2 Tumor Angiogenesis 8.3 Vascular Endothelial Growth Factor (VEGF) 8.4 Anti-Angiogenesis 8.5 Bevacizumab 8.6 Bevacizumab Toxicities 8.6.1 Hypertension 8.6.2 Reversible Posterior Leukoencephalopathy Syndrome (RPLS) 8.6.3 Proteinuria 8.6.4 Thromboembolism 8.6.5 GI Perforation (GIP) 8.6.6 Hemorrhage 8.7 Ramucirumab 8.8 Toxicities 8.9 Ramucirumab Administration, Precautions, and Monitoring Parameters 8.10 Nursing Management of Common Adverse Effects 8.10.1 Hypertension 8.10.2 Proteinuria 8.10.3 Epistaxis and Hemoptysis 8.11 Conclusion References 9: Nursing Considerations for Patients Treated with Targeted Therapies 9.1 Preparing Patients for Treatment on Targeted Therapies: Nursing Considerations 9.1.1 Access to Therapy 9.1.2 Education 9.2 Treatment Initiation and Monitoring 9.2.1 Nursing Assessment 9.2.2 Telephone Triage 9.2.3 Adherence 9.2.4 Multidisciplinary Approach 9.3 Summary References