Service Line: Rapid Response Service Version: 1.0 Publication Date: August 30, 2018 Report Length: 11 Pages

Transcription

1 CADTH RAPID RESPONSE REPORT: SUMMARY WITH CRITICAL APPRAISAL Radioembolization with yttrium-90 Microspheres for the Management of Uveal Melanoma Liver Metastases: A Review of Clinical Effectiveness and Cost- Effectiveness Service Line: Rapid Response Service Version: 1.0 Publication Date: August 30, 2018 Report Length: 11 Pages

2 Authors: Chuong Ho, Suzanne McCormack Cite As: Radioembolization with yttrium-90 microspheres for the management of uveal melanoma liver metastases: a review of clinical effectiveness and costeffectiveness. Ottawa: CADTH; 2018 Aug. (CADTH rapid response report: summary with critical appraisal). Acknowledgments: ISSN: (online) Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services. While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document. The views and opinions of third parties published in this document do not necessarily state or reflect those of CADTH. CADTH is not responsible for any errors, omissions, injury, loss, or damage arising from or relating to the use (or misuse) of any information, statements, or conclusions contained in or implied by the contents of this document or any of the source materials. This document may contain links to third-party websites. CADTH does not have control over the content of such sites. Use of third-party sites is governed by the third-party website owners own terms and conditions set out for such sites. CADTH does not make any guarantee with respect to any information contained on such third-party sites and CADTH is not responsible for any injury, loss, or damage suffered as a result of using such third-party sites. CADTH has no responsibility for the collection, use, and disclosure of personal information by third-party sites. Subject to the aforementioned limitations, the views expressed herein are those of CADTH and do not necessarily represent the views of Canada s federal, provincial, or territorial governments or any third party supplier of information. This document is prepared and intended for use in the context of the Canadian health care system. The use of this document outside of Canada is done so at the user s own risk. This disclaimer and any questions or matters of any nature arising from or relating to the content or use (or misuse) of this document will be governed by and interpreted in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the exclusive jurisdiction of the courts of the Province of Ontario, Canada. The copyright and other intellectual property rights in this document are owned by CADTH and its licensors. These rights are protected by the Canadian Copyright Act and other national and international laws and agreements. Users are permitted to make copies of this document for non-commercial purposes only, provided it is not modified when reproduced and appropriate credit is given to CADTH and its licensors. About CADTH: CADTH is an independent, not-for-profit organization responsible for providing Canada s health care decision-makers with objective evidence to help make informed decisions about the optimal use of drugs, medical devices, diagnostics, and procedures in our health care system. SUMMARY WITH CRITICAL APPRAISAL Radioembolization with Yttrium-90 for the Management of Uveal Melanoma Liver Metastasis 2

3 Context and Policy Issues Uveal melanoma is the most common primary intraocular malignancy in adults with an incidence of 5.1 per million people in the world. 1 Despite treatment of the primary tumour, over 50% of the patients with uveal melanoma develop clinical metastases over the next 30 years, with 95% of metastases occurring in the liver. 2,3 Treatment options for primary or metastatic liver tumours that are unresectable and not responsive to other therapies such as systemic chemotherapy and immunotherapy include selective internal radiotherapy with radioisotopes (SIRT), radiofrequency ablation (RFA), transarterial chemoembolization (TACE), stereotactic body radiation therapy (SBRT), proton beam therapy and molecular targeted therapy. 4-6 SIRT with yttrium-90, also known as radioembolization, is based on the administration of resin or glass microspheres loaded with the radioisotope yttrium-90, via selective arterial catheterization of tumor-feeding vessels, in order to destroy the tumour A 2015 CADTH Rapid Response report identified systematic reviews, meta-analyses, and economic evaluations on the clinical and cost-effectiveness of yttrium-90 microsphere radioembolization for the treatment of primary or secondary liver cancer, but no evidence on uveal melanoma liver metastasis was found. 11 With increasing interest in comparing the impact of SIRT to other treatment therapies such as TACE, this Rapid Response report aims to review the comparative clinical and cost-effectiveness of radioembolization with yttrium-90 microspheres versus other options for the treatment of adult patients with uveal melanoma liver metastasis. Research Question 1. What is the clinical effectiveness of radioembolization with yittrium-90 microspheres for the management of uveal melanoma liver metastases? 2. What is the cost-effectiveness of radioembolization with yittrium-90 microspheres versus other management options for the management of uveal melanoma liver metastases? Key Findings One retrospective study on patients with uveal melanoma liver metastasis compared the clinical effectiveness and toxicity of SIRT using yttrium-90 microspheres to a historical control group using systemic chemotherapy. Patients on SIRT both as first-line therapy or following failed systemic chemotherapy - had a statistically significant improvement in median overall survival time compared to those on historical systemic chemotherapy, and this effect was larger in the group of patients who received SIRT as first-line treatment. Most treatment-related side effects on patients with SIRT were mild and self-limited, and were more pronounced in patients with systemic chemotherapy. These findings from limited evidence need to be treated cautiously. There was no relevant evidence found on the costeffectiveness of radioembolization with yittrium-90 microspheres versus other management options for the management of uveal melanoma liver metastases. SUMMARY WITH CRITICAL APPRAISAL Radioembolization with Yttrium-90 for the Management of Uveal Melanoma Liver Metastasis 3

4 Methods This report makes use of a literature search strategy developed for a previous CADTH report. For the current report, a limited literature search was conducted on key resources including PubMed, OVID, the Cochrane Library, University of York Centre for Reviews and Dissemination (CRD) databases, Canadian and major international health technology agencies, as well as a focused Internet search. No filters were applied to limit retrieval by study type. Where possible, retrieval was limited to the human population. The search was limited to English-language documents published between January 1, 2015 and July 26, 2018 to capture any articles published since the previous report. Rapid Response reports are organized so that the evidence for each research question is presented separately. Literature Search Methods Rapid Response reports are organized so that the evidence for each research question is presented separately. Selection Criteria and Methods One reviewer screened citations and selected studies. In the first level of screening, titles and abstracts were reviewed and potentially relevant articles were retrieved and assessed for inclusion. The final selection of full-text articles was based on the inclusion criteria presented in Table 1. Table 1: Selection Criteria Population Intervention Comparator Outcomes Adult patients with unresectable uveal melanoma liver metastases Intra-tumoural administration of yttrium-90 (Y-90) microspheres. Applied alone or in combination with transarterial chemoembolization (TACE) or systemic chemotherapy Q1 Q2: Other palliative options, other cancer treatment options Q1: Placebo Q1. Tumour size reduction, time to progression, progression rate, survival rate (progression free survival, overall survival), quality of life; Toxicity, adverse events, discontinuation Study Designs Q2. Cost-effectiveness Heath technology assessments (HTAs), systematic reviews (SRs) and meta-analyses (MAs), randomized controlled trials (RCTs), non-rcts, economic evaluations Exclusion Criteria Articles were excluded if they did not meet the selection criteria outlined in Table 1, they were duplicate publications, or were published prior to Critical Appraisal of Individual Studies The included clinical study was critically appraised using the Downs and Black instrument. 12 A summary score was not calculated for the included study; rather, a review of the strengths and limitations was described. SUMMARY WITH CRITICAL APPRAISAL Radioembolization with Yttrium-90 for the Management of Uveal Melanoma Liver Metastasis 4

5 Summary of Evidence Quantity of Research Available A total of 491 citations were identified in the literature search. Following screening of titles and abstracts, 487 citations were excluded and four potentially relevant reports from the electronic search were retrieved for full-text review. No potentially relevant publications were retrieved from the grey literature search. Of these potentially relevant articles, three publications were excluded for various reasons, while one publication met the inclusion criteria and was included in this report. Appendix 1 presents the PRISMA flowchart of the study selection. Summary of Study Characteristics A detailed summary of the included study is provided in Appendix 2. Study Design The clinical study included in this review is an observational retrospective study, with a historical control group. 13 Country of Origin The study was conducted in Finland. 13 Patient Population The intervention group included 18 adult patients (36 72 years) with uveal melanoma liver metastasis, in which 14 received SIRT and four received systemic chemotherapy as their initial treatment. 13 The historical control group included eight adult patients with uveal melanoma liver metastasis who had received systemic chemotherapy. Interventions and Comparators The clinical study compared SIRT using yttrium-90 microspheres as first and second line treatment with historical control using systemic chemotherapy (mostly dacarbazine). 13 Outcomes The clinical study examined overall survival time (in months) and treatment-related toxicity such as increase in transaminase levels, nausea, abdominal pain. 13 Summary of Critical Appraisal Details of the strengths and limitations of the included study are summarized in Appendix 3. The included clinical study 13 is an observational retrospective cohort study which has limitations by nature such as selection bias (sample may not be representative of the population intended to be analyzed) and recall bias (data may not be accurate); the hypotheses were clearly described, the method of selection from the source population and representation were described, losses to follow-up were reported, main outcomes, interventions, patient characteristics, and main findings were clearly described, and estimates of random variability and actual probability values were provided. The study did not perform calculations to determine that it was adequately powered to detect a clinically important effect. Assessors and patients were not blinded to treatment assignment in the study which may have impacted the objectivity of the outcome assessments. The internal SUMMARY WITH CRITICAL APPRAISAL Radioembolization with Yttrium-90 for the Management of Uveal Melanoma Liver Metastasis 5

6 validity of the study was limited by the nature of the retrospective study and the use of a historical control group that is prone to selection bias. The small number of included patients limits the generalizability of the findings to all people with uveal melanoma liver metastasis. Summary of Findings Clinical Effectiveness The included study examined the clinical effectiveness and toxicity of SIRT using yttrium-90 microspheres compared to a historical control group who had received systemic chemotherapy. 13 Patients on SIRT both as first-line therapy or following failed systemic chemotherapy - had a median overall survival time (OS) of 13.5 months while the historical chemotherapy cohort had a median OS of 10.5 months (the difference was statistically significant). Subgroup analysis showed that patients who received SIRT as a first-line treatment had an OS of 18.7 months (the difference with the historical chemotherapy cohort was statistically significant). Most side effects in the SIRT group were mild and self-limited; the chemotherapy group had more pronounced treatment-related side effects such as nausea, infections, declining performance status, and liver and hematological toxicity (numbers and P values not provided). The authors concluded that SIRT is a feasible and safe treatment option for patients with uveal melanoma liver metastasis. Further detail is included in Appendix 4. Cost-Effectiveness No relevant studies were identified or included regarding the cost-effectiveness of radioembolization with yittrium-90 microspheres versus other management options for the management of uveal melanoma liver metastases. Limitations This review is limited by the sparsity of the evidence. One retrospective cohort study examining the comparative clinical effectiveness of radioembolization with yittrium-90 microspheres versus systemic chemotherapy for the management of uveal melanoma liver metastases was included. The ability to draw firm conclusions is therefore limited. Conclusions and Implications for Decision or Policy Making Evidence from one retrospective non-randomized study indicates that patients on SIRT both as first-line therapy and following failed systemic chemotherapy - had a statistically significant improvement in median overall survival time compared to a historic cohort who received systemic chemotherapy for the management of uveal melanoma liver metastasis. The effect was larger in the group of patients who received SIRT as first-line treatment. Most treatment-related side effects reported by the patients on SIRT were mild and selflimited, and systemic chemotherapy was associated with more pronounced side effects. RCTs with head-to-head comparisons between SIRT and other management options such as TACE or systemic chemotherapy would reduce the uncertainty regarding the comparative effectiveness and efficacy of SIRT for the treatment of uveal melanoma liver metastasis. Cost-effectiveness studies comparing SIRT and other management options in a Canadian context are needed to help decision makers weigh the costs and benefits of SIRT. SUMMARY WITH CRITICAL APPRAISAL Radioembolization with Yttrium-90 for the Management of Uveal Melanoma Liver Metastasis 6

7 References 1. Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology. 2011;118(9): Kujala E, Mäkitie T, Kivelä T. Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci. 2003;44(11): Diener-West M, Reynolds SM, Agugliaro DJ, et al. Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. Arch Ophthalmol. 2005;123(12): Eggert T, Greten TF. Current standard and future perspectives in non-surgical therapy for hepatocellular carcinoma. Digestion. 2017;96(1): Carvajal RD. Management of metastatic uveal melanoma. In: Post TW, ed. UpToDate. Waltham (MA): UpToDate; 2018: Accessed 2018 Aug Curley SA. Nonsurgical therapies for localized hepatocellular carcinoma. In: Post TW, ed. UpToDate. Waltham (MA): UpToDate; 2018: Accessed 2018 Aug Nasser F, Motta Leal Filho JM, Affonso BB, et al. Liver metastases in pancreatic acinar cell carcinoma treated with selective internal radiation therapy with Y-90 resin microspheres. Case Reports Hepatol. 2017;2017: Joo I, Kim HC, Kim GM, Paeng JC. Imaging evaluation following (90)Y radioembolization of liver tumors: what radiologists should know. Korean J Radiol. 2018;19(2): Khajornjiraphan N, Thu NA, Chow PK. Yttrium-90 microspheres: a review of its emerging clinical indications. Liver cancer. 2015;4(1): Affonso BB, Motta-Leal-Filho JMD, Cavalcante FA, Jr., et al. Aspects of images in magnetic resonance of liver tumors treated with transarterial selective internal radiotherapy with yttrium-90. Einstein (Sao Paulo, Brazil). 2018;16(1):eRC Yttrium-90 microsphere radioembolization for the treatment of primary or secondary liver cancer: clinical effectiveness, cost-effectiveness, and guidelines. (CADTH Rapid response report: summary of abstracts). Ottawa (ON): CADTH; Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health. 1998;52(6): Accessed 2018 Aug Tulokas S, Maenpaa H, Peltola E, et al. Selective internal radiation therapy (SIRT) as treatment for hepatic metastases of uveal melanoma: a Finnish nation-wide retrospective experience. Acta Oncol. 2018:1-8. SUMMARY WITH CRITICAL APPRAISAL Radioembolization with Yttrium-90 for the Management of Uveal Melanoma Liver Metastasis 7

8 Appendix 1: Selection of Included Studies 491 citations identified from electronic literature search and screened 387 citations excluded 4 potentially relevant articles retrieved for scrutiny 0 potentially relevant report retrieved from other sources (grey literature, hand search) 4 potentially relevant reports 3 reports excluded: -irrelevant population (2) -irrelevant comparator (1) 1 report included in review SUMMARY WITH CRITICAL APPRAISAL Radioembolization with Yttrium-90 for the Management of Uveal Melanoma Liver Metastasis 8

9 Appendix 2: Characteristics of Included Publications Table 2: Characteristics of Included Clinical Study First author, year, country Tulokas, , Finland Study design, objectives Observational retrospective study with historical control group To assess the clinical effectiveness of SIRT in patients with uveal melanoma liver metastasis SIRT = selective internal radiation therapy Intervention Comparators SIRT using yttrium-90 microspheres Historical systemic chemotherapy (mostly dacarbazine) Patients SIRT group: 18 adult patients with uveal melanoma liver metastasis who had a predicted life expectancy of more than 3 months (14 patients had SIRT as first-line therapy; 4 patients received systemic chemotherapy prior to SIRT) Historical control group: 8 adult patients with uveal melanoma liver metastasis Main study outcomes Overall survival time Toxicity SUMMARY WITH CRITICAL APPRAISAL Radioembolization with Yttrium-90 for the Management of Uveal Melanoma Liver Metastasis 9

10 Appendix 3: Critical Appraisal of Included Publications Table 3: Strengths and Limitations of Clinical Study using Downs and Black 12 Strengths hypothesis clearly described method of selection from source population and representation described loss to follow-up reported main outcomes, interventions, patient characteristics, and main findings clearly described estimates of random variability and actual probability values provided Tulokas 13 Limitations observational retrospective study with historical control group power calculation to detect a clinically important effect not performed SUMMARY WITH CRITICAL APPRAISAL Radioembolization with Yttrium-90 for the Management of Uveal Melanoma Liver Metastasis 10

11 Appendix 4: Main Study Findings and Authors Conclusions Table 4: Summary of Findings of Included Studies Main Study Findings Clinical effectiveness: OS (median) All patients (n = 18) SIRT: 13.5 (range, ) months Chemotherapy: 10.5 (range, ) months. P = Patients who received SIRT as first-line treatment (n = 14) SIRT: 18.7 (range ) months Chemotherapy: 10.5 (range ) months. P = Toxicity (all patients) SIRT No treatment-related deaths Grade 1 2 increase of transaminases: 11 patients Grade 3 and one had grade 4 transaminase elevation: 1 patient Other mild, self-limited toxicity (grade 1 2) including nausea, abdominal discomfort/pain, tiredness and subfebrility: 15 patients Hospitalized due to fever (38.7 C, grade 1) related to liver toxicity: 1 patient Chemotherapy group had more pronounced treatmentrelated side effects such as nausea, infections, declining performance status, liver and hematological toxicity (figures and P values not provided) OS = overall survival time; SIRT = selective internal radiation therapy Tulokas 13 Authors Conclusion SIRT is a feasible and safe treatment for liver metastases in patients with uveal melanoma (p 1) SUMMARY WITH CRITICAL APPRAISAL Radioembolization with Yttrium-90 for the Management of Uveal Melanoma Liver Metastasis 11