Ceritinib for Untreated Anaplastic Lymphoma Kinase-Positive Advanced Non-Small-Cell Lung Cancer: An Evidence Review Group Evaluation of a NICE Single Technology Appraisal
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The National Institute for Health and Care Excellence (NICE) invited the company that manufactures ceritinib (Zykadia®, Novartis) to submit evidence on the clinical and cost effectiveness of the drug, as a first-line treatment for adults with anaplastic lymphoma kinase (ALK)-positive (+) advanced non-small-cell lung cancer (NSCLC), as part of the Institute’s single technology appraisal (STA) process. The CRD (Centre for Reviews and Dissemination) and CHE (Centre for Health Economics) Technology Assessment Group at the University of York was commissioned to act as the Evidence Review Group (ERG). This paper describes the Company’s submission (CS), the ERG review and NICE’s subsequent decisions. The evidence submitted in support of ceritinib, as the first-line treatment in ALK+ advanced NSCLC, was a phase III, international, multicentre, open-label randomised controlled trial (RCT) comparing ceritinib with pemetrexed/cisplatin plus pemetrexed maintenance therapy (chemotherapy [CT] group). The results indicated that ceritinib prolonged progression-free survival (PFS) compared with CT. The only comparator considered in the CS was crizotinib. The evidence selected in support of crizotinib was PROFILE 1014, an open-label RCT of crizotinib, compared with pemetrexed/cisplatin CT (without maintenance therapy), in previously untreated advanced or metastatic ALK+ NSCLC. The design and population of PROFILE 1014 was similar to that of ASCEND-4, though there were some differences between the trials. The Company considered it not possible to perform an ‘anchor-based’ analysis of first-line ceritinib and crizotinib, and presented a Matching-Adjusted Indirect Comparison (MAIC) of ceritinib and crizotinib using only the ALK inhibitor arm of ASCEND-4 and PROFILE 1014. The indirect comparison suggests that ceritinib may be more effective in prolonging PFS than crizotinib. The ERG agreed that an indirect comparison using only the ALK inhibitor arm of the trials was the only option available in the present assessment; however, a number of limitations and potential bias were identified in this analysis. The Company’s model estimated that ceritinib was cost effective when compared with crizotinib. However, the ERG highlighted several concerns with the Company’s analysis; the ERG’s preferred base case estimated an incremental cost-effectiveness ratio of £69,255 per quality-adjusted life-year (no patient access scheme [PAS] included). The ERG considered the economic analysis to be sensitive to changes in assumption used, partly due to the due to the immaturity of the overall survival data from trials, which leads to uncertainty around the extrapolation used. The NICE Appraisal Committee concluded that ceritinib is recommended, within its marketing authorisation, as an option for untreated ALK+ advanced NSCLC in adults, if the Company provides it with the discount agreed in the PAS.
The ERG would like to thank Professor Michael Lind, Consultant Clinical Oncologist, Castle Hill Hospital and the Hull York Medical School, who acted as a clinical expert advisor to the ERG.
LC, JOC, NW, KW and RH all formed part of the ERG that produced the ERG report that this paper describes. JOC wrote the first draft of the manuscript. All authors commented on the manuscript and approved the final version. This summary has not been externally reviewed by PharmacoEconomics.
Compliance with Ethical Standards
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme (project number 16/134/13) [see the HTA programme website (http://www.hta.ac.uk) for further project information]. This summary of the ERG report was compiled after the Appraisal Committee’s review, and incorporates additional information and comment from the authors on the STA process and iterations of the NICE guidance not covered by the HTA report.
Conflict of interest
LC, JOC, NW, KW and RH report no conflicts of interest that are directly relevant to the content of this summary.
- 1.National Institute for Health and Care Excellence. Ceritinib for untreated anaplastic lymphoma kinase-positive non-small cell lung cancer [TA500]. Document B. Company evidence submission. London: NICE; 2017. https://www.nice.org.uk/guidance/ta500/documents/committee-papers. Accessed 5 Oct 2017.
- 2.National Institute for Health and Care Excellence. Ceritinib for untreated anaplastic lymphoma kinase-positive advanced non-small-cell lung cancer [TA500]. Evidence Review Group’s Report. London: NICE; 2017. https://www.nice.org.uk/guidance/ta500/documents/committee-papers. Accessed 5 Oct 2017.
- 3.Royal College of Physicians. National Lung Cancer Audit annual report 2016 (for the audit period 2015): Healthcare Quality Improvement Partnership; 2017. https://www.rcplondon.ac.uk/projects/outputs/nlca-annual-report-2016. Accessed 5 Oct 2017.
- 11.National Institute for Health and Care Excellence. Crizotinib for untreated anaplastic lymphoma kinase-positive non-small-cell lung cancer [TA406]. Committee Papers. London: NICE; 2016. https://www.nice.org.uk/guidance/ta406/documents/committee-papers. Accessed 5 Oct 2017.
- 12.National Institute for Health and Care Excellence. Ceritinib for previously treated anaplastic lymphoma kinase positive nonsmall-cell lung cancer [TA395]. London: NICE; 2016. https://www.nice.org.uk/guidance/ta395/resources/ceritinib-for-previously-treated-anaplastic-lymphoma-kinase-positive-nonsmallcell-lung-cancer-pdf-82602911852485. Accessed 5 Oct 2017.
- 16.European Medicines Agency. Zykadia: Summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003819/WC500187504.pdf. Accessed 5 Oct 2017.
- 21.Blackhall F, Kim DW, Besse B, Nokihara H, Han JY, Wilner KD, et al. Patient-reported outcomes and quality of life in PROFILE 1007: a randomized trial of crizotinib compared with chemotherapy in previously treated patients with ALK-positive advanced non-small-cell lung cancer. J Thorac Oncol. 2014;9(11):1625–33.CrossRefGoogle Scholar
- 22.Chouaid C, Agulnik J, Goker E, Herder GJ, Lester JF, Vansteenkiste J, et al. Health-related quality of life and utility in patients with advanced non-small-cell lung cancer: a prospective cross-sectional patient survey in a real-world setting. J Thorac Oncol. 2013;8(8):997–1003.CrossRefGoogle Scholar
- 23.Felip E, Orlov S, Park K, Yu C-J, Tsai C-M, Nishio M, et al. ASCEND-3: A single-arm, open-label, multicenter phase II study of ceritinib in ALKi-naïve adult patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC) [abstract no. 8060]. J Clin Oncol. 2015;33(15 Suppl):8060.Google Scholar
- 24.NHS Reference Costs 2015-2016. National Schedule of Reference Costs: The main schedule. https://www.gov.uk/government/publications/nhs-reference-costs-2015-to-2016.
- 25.National Institute for Health and Care Excellence. Ceritinib for untreated ALK-positive non-small cell lung cancer [TA500]. Final appraisal determination. London: NICE; 2017. https://www.nice.org.uk/guidance/ta500/documents/final-appraisal-determination-document. Accessed 5 Oct 2017.