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Single Technology Appraisal Tivozanib for Treating Renal Cell Carcinoma Final Scope, 2017

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Single Technology Appraisal Tivozanib for Treating Renal Cell Carcinoma Final Scope, 2017 Single Technology Appraisal Tivozanib for treating renal cell carcinoma [ID591] Committee Papers © National Institute for Health and Care Excellence 2017. All rights reserved. See Notice of Rights. The content in this publication is owned by multiple parties and may not be re-used without the permission of the relevant copyright owner. NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE SINGLE TECHNOLOGY APPRAISAL Tivozanib for treating renal cell carcinoma [ID591] Contents: 1. Pre-Meeting Briefing 2. Final Scope and Final Matrix of Consultees and Commentators 3. Company submission from Eusapharma 4. Clarification letters NICE request to the company for clarification on their submission NICE additional clarification questions Company response to NICE’s request for clarification Company IPCW analysis report Company RPSFT report Additional analysis results Scenario anyalyis results 5. Patient group, professional group and NHS organisation submission from: Kidney Cancer Support Network Kidney Cancer UK Royal College of Physicians on behalf of the NCRI-ACP-RCP-RCR 6. Expert statements from: Professor Peter Clark - NHS commissioning expert statement Dr Paul Nathan - clinical expert statement - nominated by the NCRI- ACP-RCP-RCR Professor John Wagstaff – clinical expert statement - nominated by the EUSA Pharma Lucy Willingale – patient expert statement nominated by the Kidney Cancer UK 7. Evidence Review Group report prepared by BMJ Group Evidence Review Group report Erratum 8. Evidence Review Group report – factual accuracy check Any information supplied to NICE which has been marked as confidential, has been redacted. All personal information has also been redacted. © National Institute for Health and Care Excellence 2017. All rights reserved. See Notice of Rights. The content in this publication is owned by multiple parties and may not be re-used without the permission of the relevant copyright owner. Pre-meeting briefing Tivozanib for treating renal cell carcinoma This slide set is the pre-meeting briefing for this appraisal. It has been prepared by the technical team with input from the committee lead team and the committee chair. It is sent to the appraisal committee before the committee meeting as part of the committee papers. It summarises: • the key evidence and views submitted by the company, the consultees and their nominated clinical experts and patient experts and • the Evidence Review Group (ERG) report It highlights key issues for discussion at the first appraisal committee meeting and should be read with the full supporting documents for this appraisal Please note that this document includes information from the ERG before the company has checked the ERG report for factual inaccuracies The lead team may use, or amend, some of these slides for their presentation at the Committee meeting 1 Abbreviation In full AE Adverse event CHMP Committee for Medicinal Products for Human Use DIC Deviance information criterion ECOG Eastern Cooperative Oncology Group EQ-5D EuroQol five dimensions questionnaire ERG Evidence review group FP Fractional polynomial HR Hazard ratio HRQoL Health related quality of life ICER Incremental cost-effectiveness ratio IFN Interferon IPCW Inverse probability of censoring weights ITT Intention to treat KM Kaplan-Meier MAIC Matched adjusted indirect comparison MSKCC Memorial Sloan Kettering Cancer Center mTOR Mammalian target of rapamycin NMA Network meta-analysis OS Overall survival PAS Patient access scheme PFS Progression-free survival QALY Quality-adjusted life year RCC Renal cell carcinoma RDI Relative dose intensity RPSFT Rank preserving structural failure time TKI Tyrosine kinase inhibitor 2 VEGF(R) Vascular endothelial growth factor (receptor) Key issues – clinical effectiveness • Where will tivozanib be used in the treatment pathway?: – treatment-naive population (1st line) • Is the clinical trial TIVO-1 generalisable to UK practice in terms of baseline characteristics? • Is the analysis using treatment-naive patients or the whole trial population most relevant? • Do overall survival results in geographical subgroups support effectiveness of tivozanib in UK? • What is the most appropriate method for crossover adjustment (IPCW, RPSFT, other [MAIC])? – Does the proportional hazards assumption hold? • What is the most appropriate approach for extrapolation (e.g. fractional polynomial method, other)? • Are results from the network meta-analysis plausible? – Are the other trials in the network generalisable to NHS clinical practice? – Should the trials be adjusted for crossover? • Is tivozanib clinically effective? 3 Disease background and management Kidney cancer • More common in men than women • Five-year survival is 56%, varying with age • 86% of renal cancers are renal cell carcinoma Renal cell carcinoma • Estimated 9,045 new diagnoses in England per year • Disease is often locally advanced or metastatic at point of diagnosis • Early stage disease can be treated surgically – half of patients who have surgical treatment will develop metastatic disease • Overall survival for people with metastatic disease is 8 months to 3.6 years 4 Tivozanib (Fotivda) EUSAPharma UK marketing First line treatment of adult patients with advanced authorisation renal cell carcinoma (RCC) and for adult patients who are VEGFR and mTOR pathway inhibitor-naïve following disease progression after one prior treatment with cytokine therapy for advanced RCC Administration Oral therapy Mechanism of Tyrosine kinase inhibitor with affinity for all three action vascular endothelial growth factor receptors, leading to reduced vascularisation of tumours Dosage 1,340 micrograms (one tablet) tivozanib once daily for 21 days, followed by a 7-day rest period 890 micrograms capsule is available so that the dose can be reduced if necessary 5 Decision problem Final scope issued by Company’s decision NICE problem Population Adults with recurrent or Adults with recurrent or metastatic renal cell metastatic RCC carcinoma (RCC) Outcome • Overall survival • Overall survival • Progression-free survival • Progression-free survival • Response rates • Response rates • Adverse effects of • Adverse effects of treatment treatment • Health-related quality of life Company states there is insufficient data from trials for independent analysis of health-related quality of life 6 Decision problem Final scope issued by NICE Company’s decision problem Comparator Untreated disease: Untreated disease: • Sunitinib • Sunitinib • Pazopanib • Pazopanib • Immunotherapy (interferon- • Immunotherapy alfa, interleukin-2) (interferon-alfa, Previously treated disease: interleukin-2) •Axitinib • Nivolumab • Everolimus • Cabozantinib • Best supportive care • Company: Tivozanib will not be used for previously-treated disease in NHS clinical practice • Marketing authorisation for tivozanib as 2nd line is for use after 7 immunotherapy, which is not used in UK Current treatment pathway 8 Sunitinib Pazopanib 1st Tivozanib ★ ★ line ★ TA169 TA215 Tivozanib nd 2 Only after Axitinib Cabo- Lenvatinib+ line immuno- ★ therapy Nivolumab zantinib Everolimus TA333 (subject to (subject to Note: Only after ongoing ongoing company did cytokine TA417 guidance) guidance) 3rd not submit or ★ ★ line evidence for sunitinib this position 4th Everolimus ✪ line TA432 Only after VEGF-targeted therapy Key; VEGF, vascular endothelial growth factor ★: oral tyrosine kinase inhibitors; ✪: oral mammalian target of rapamycin (mTOR) inhibitor; : anti-programmed death 1 (PD-1) inhibitor Comments from patient and professional • Patient groups groups – People may experience constant pain as well as psychological effects e.g. depression, loss of confidence and self-worth – Many patients have to give up work due to debilitating effects of disease and treatments available – leads to financial pressures – Few treatment options available currently and adverse effects are significant e.g. extreme fatigue, severe hand and foot syndrome, chronic diarrhoea – No biomarkers to predict who will respond to each drug, therefore range of treatment options important • Professional groups – Sunitinib or pazopanib currently used first line (sorafenib not used first line in UK) – Concern about study design, crossover rates and lack of a standard of care comparator in the first line setting in TIVO-1 study – Adverse event profile of tivozanib is comparable with other TKIs 9 ERG comments Agree with company about the appropriate comparators • Agree that cytokines (immunotherapy) are not a relevant comparator for untreated disease as rarely used in UK • Agree that axitinib, nivolumab, everolimus, cabozantinib and best supportive care are not relevant comparators given the evidence submitted and proposed marketing authorisation 10 Company’s clinical evidence Tivozanib vs sorafenib: TIVO-1 trial (n=517) Patients Tivozanib Endpoints 1.5 mg oral daily for 3 • ≥18 years weeks, 1 week off 1° • Progression-free • Advanced or Open-label RCT survival metastatic RCC 1:1 randomisation (independent • Treatment-naive Treatment until no review - blinded) patients or patients clinical benefit or with one prior intolerable toxicity 2° systemic treatment • Overall survival for metastatic RCC Patients could cross • Overall response over to tivozanib on rate progression • Safety • Health-related Sorafenib quality of life 400 mg oral twice per day RCT, randomised controlled trial; HR, hazard ratio; OR, odds ratio 11 Company’s clinical evidence Extension study 902 • Extension study AV-951-09-902 “902” – allowed long-term access
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