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Eunethta Joint Action 3 WP4 ALECTINIB AS MONOTHERAPY EUnetHTA Joint Action 3 WP4 Rapid assessment of pharmaceutical technologies using the HTA Core Model® for Rapid Relative Effectiveness Assessment ALECTINIB AS MONOTHERAPY FOR THE FIRST-LINE TREATMENT OF ADULT PATIENTS WITH ALK-POSITIVE ADVANCED NON-SMALL CELL LUNG CANCER Project ID: PTJA03 Version 1.3, 22th January 2018 Dec2015 ©EUnetHTA, 2015. Reproduction is authorised provided EUnetHTA is explicitly acknowledged1 PTJA03 - Alectinib as monotherapy for the first line treatment of ALK-positive advanced NSCLC DOCUMENT HISTORY AND CONTRIBUTORS Version Date Description V1.0 24/11/2017 First draft. V1.1 18/12/2017 Input from coauthors and dedicated reviewers has been processed. V1.2 04/01/2018 Input from medical editor has been processed. V1.3 22/01/2019 Input from manufacturer has been processed. Disclaimer The assessment represents a consolidated view of the EUnetHTA assessment team members and is in no case the official opinion of the participating institutions or individuals. EUnetHTA Joint Action 3 is supported by a grant from the European Commission. The sole responsibility for the content of this document lies with the authors, and neither the European Commission nor EUnetHTA are responsible for any use that may be made of the information contained therein. Assessment team Author(s) Dental and Pharmaceutical Benefits Agency (TLV), Sweden Coauthor(s) Main Association of Austrian Social Security Institutions (HVB), Austria Agency for Quality and Accreditation in Health Care and Social Welfare (AAZ), Croatia Dedicated National Institute for Health and Care Excellence (NICE), United Kingdom Reviewer(s) Regione Veneto, Italy Andalusian Agency for Health Technology Assessment (AETSA), Spain National Institute of Pharmacy and Nutrition (NIPN), Hungary Ministry of Health (MoH), Malta (observer) Consultation of the draft rapid assessment Manufacturer(s) [v1.2] Roche (factual accuracy check) Medical editor [v1.1]] Compuscript Ltd Conflict of interest All authors and dedicated reviewers involved in the production of this assessment have declared they have no conflicts of interest in relation to the technology assessed according to the EUnetHTA declaration of interest and confidentiality undertaking form. How to cite this assessment Please cite this assessment as follows: Dental and Pharmaceutical Benefits Agency (TLV), Main Association of Austrian Social Security Institutions (HVB), Agency for Quality and Accreditation in Health Care and Social Welfare (AAZ). Rapid assessment on pharmaceutical technologies using the HTA Core Model for Rapid Relative Effectiveness Assessment. Alectinib as monotherapy for the first-line treatment of adult patients with ALK-positive advanced non-small cell lung cancer. EUnetHTA Project ID: PTJA03. 2017. Version 1.3, 22th January 2018 EUnetHTA Joint Action 3 WP4 2 PTJA03 - Alectinib as monotherapy for the first line treatment of ALK-positive advanced NSCLC TABLE OF CONTENTS SUMMARY OF RELATIVE EFFECTIVENESS OF ALECENSA (ALECTINIB) ............................. 8 1 SCOPE ..................................................................................................................................... 16 2 METHODS AND EVIDENCE INCLUDED ............................................................................... 18 2.1 ASSESSMENT TEAM ............................................................................................................ 18 2.2 SOURCE OF ASSESSMENT ELEMENTS .................................................................................. 18 2.3 SEARCH ............................................................................................................................. 18 2.4 STUDY SELECTION .............................................................................................................. 19 2.5 DATA EXTRACTION AND ANALYSES ...................................................................................... 20 2.6 QUALITY RATING ................................................................................................................ 21 2.7 PATIENT INVOLVEMENT ....................................................................................................... 22 2.8 DESCRIPTION OF THE EVIDENCE USED ................................................................................. 23 2.9 DEVIATIONS FROM PROJECT PLAN ....................................................................................... 23 3 DESCRIPTION AND TECHNICAL CHARACTERISTICS OF TECHNOLOGY (TEC) ........... 24 3.1 RESEARCH QUESTIONS ....................................................................................................... 24 3.2 RESULTS ........................................................................................................................... 24 4 HEALTH PROBLEM AND CURRENT USE OF THE TECHNOLOGY (CUR) ....................... 29 4.1 RESEARCH QUESTIONS ....................................................................................................... 29 4.2 RESULTS ........................................................................................................................... 29 5 CLINICAL EFFECTIVENESS .................................................................................................. 33 5.1 RESEARCH QUESTIONS ....................................................................................................... 33 5.2 RESULTS ........................................................................................................................... 33 6 SAFETY ................................................................................................................................... 50 6.1 RESEARCH QUESTIONS ....................................................................................................... 50 6.2 RESULTS ........................................................................................................................... 50 7 PATIENT INVOLVEMENT ....................................................................................................... 58 8 DISCUSSION ........................................................................................................................... 60 9 CONCLUSION ......................................................................................................................... 63 APPENDIX 1. EXTRAPOLATION OF PFS AND OS/SURVIVAL ANALYSIS ............................. 64 INTRODUCTION ........................................................................................................................... 64 MODEL DESCRIPTION ................................................................................................................. 65 SELECTION OF PARAMETRIC FUNCTION ....................................................................................... 68 RESULTS FOR PREFERRED EXTRAPOLATION MODELS .................................................................. 71 APPENDIX 2: METHODS AND DESCRIPTION OF THE EVIDENCE USED .............................. 78 DOCUMENTATION OF THE SEARCH STRATEGIES ........................................................................... 78 DESCRIPTION OF THE EVIDENCE USED ....................................................................................... 93 APPENDIX 3: REGULATORY AND REIMBURSEMENT STATUS ........................................... 124 APPENDIX 4: CHECKLIST FOR POTENTIAL ETHICAL, ORGANISATIONAL, PATIENT AND SOCIAL AND LEGAL ASPECTS ................................................................ 132 APPENDIX 5. HEALTH-RELATED QUALITY OF LIFE ............................................................. 133 APPENDIX 6. INDIRECT COMPARISONS – STATISTICAL ASPECTS ................................... 135 GENERAL REMARKS .................................................................................................................. 135 10 REFERENCES ....................................................................................................................... 144 Version 1.3, 22th January 2018 EUnetHTA Joint Action 3 WP4 3 PTJA03 - Alectinib as monotherapy for the first line treatment of ALK-positive advanced NSCLC LIST OF TABLES AND FIGURES Tables Table 0.1. Summary of findings for alectinib, primary analysis 9 February 2017 .......................... 13 Table 1.1. Scope according to population, intervention, comparison, outcomes and study design analysis........................................................................................................................................... 16 Table 2.1. Main characteristics of studies included ....................................................................... 23 Table 3.1. Features of the intervention and comparators .............................................................. 25 Table 3.2. Administration and dosing of the intervention and comparators ................................... 25 Table 4.1 Estimated incidence of (ALK-positive) NSCLC in Europe in 2012 ................................. 32 Table 5.1. Research questions and element IDs ........................................................................... 33 Table 5.2. Baseline characteristics of patients across relevant studies ......................................... 36 Table 5.3. Overall survival .............................................................................................................. 37 Table 5.4. Progression-free survival by investigator and independent review committee assessments for alectinib versus crizotinib in the ALEX trial (intent-to-treat
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