Everolimus, lutetium-177 DOTATATE and sunitinib for advanced, unresectable or metastatic neuroendocrine tumours with disease progression: a systematic review and cost-effectiveness analysis

Mújica-Mota, Rubén; Varley-Campbell, Jo; Tikhonova, Irina A.; Cooper, C; Griffin, Ed; Haasova, Marcela; Peters, Jaime; Lucherini, S.; Talens-Bou, Juan; Long, Linda; Sherriff, David; Napier, Mark; Ramage, John; Hoyle, Martin

doi:10.3310/hta22490

Cited by 22 publications

(34 citation statements)

References 157 publications

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“…The lack of cost data collected from relevant patient population remains the main weakness of existing evidence from HEEs. Another limitation relates to the lack of data on medium to long term survival outcomes and therefore the need to rely on clinical expert opinion for predicting those outcomes beyond one or two years after the start of targeted therapies, particularly in gastrointestinal NEN [41].…”

Section: Discussionmentioning

confidence: 99%

“…This leads to confounding in post-progression endpoints, for example overall survival, and renders estimates of these endpoints unsuitable for inclusion in economic models without some form of adjustment. The rank-preserving structural failure time (RPSFT) method was used in three included studies [26,41,54] to adjust for this confounding, but this method typically assumes that the treatment effect received by switchers must be the same as the treatment effect in those initially randomised to the study drug, which is unlikely to be true when the main cause for switching is disease progression. Alternative methods for adjusting for treatment switching (such as the inverse probability of censoring weights, IPCW, method), as well as intention-to-treat analyses should be conducted and presented.…”

Section: Discussionmentioning

confidence: 99%

“…This suggests longitudinal preference based assessment of quality of life outcomes of NEN, based on representative patient cohorts, is needed. This evidence would help distinguish patient preferences and relative effectiveness between targeted therapies in advanced or metastatic pancreatic NETs which have similar clinical outcomes but different safety profiles [41].…”

Section: Discussionmentioning

confidence: 99%

“…Mujica-Mota et al [41] developed a partitioned survival model to conduct a cost-utility analysis of sunitinib, everolimus, and 177 Lu-DOTATATE versus BSC in patients with advanced unresectable or metastatic NET. The measure of benefit was QALYs and costs were included from an NHS and personal social services perspective.…”

Section: Somatostatin Analogues (Ssas)mentioning

confidence: 99%

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Evaluating cost-effectiveness in the management of neuroendocrine neoplasms

White

Mújica-Mota

Snowsill

et al. 2020

Rev Endocr Metab Disord

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The rapid evolution of novel, costly therapies for neuroendocrine neoplasia (NEN) warrants formal high-quality cost-effectiveness evaluation. Costs of individual investigations and therapies are high; and examples are presented. We aimed to review the last ten years of standalone health economic evaluations in NEN. Comparing to published standards, EMBASE, Cochrane library, Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database and the Health Technology Assessment (HTA) Database were searched for health economic evaluations (HEEs) in NEN published between 2010 and October 2019. Of 12 economic evaluations, 11 considered exclusively pharmacological treatment (3 studies of SSAs, 7 studies of sunitinib, everolimus and/or 177Lu-DOTATATE and 1 study of telotristat ethyl) and 1 compared surgery with intraarterial therapy. 7 studies of pharmacological treatment had placebo or best supportive care as the only comparator. There remains a paucity of economic evaluations in NEN with the majority industry funded. Most HEEs reviewed did not meet published health economic criteria used to assess quality. Lack of cost data collected from patient populations remains a significant factor in HEEs where clinical expert opinion is still often substituted. Further research utilizing high-quality effectiveness data and rigorous applied health economic analysis is needed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Somatostatin Analogues (Ssas)mentioning

confidence: 99%

See 2 more Smart Citations

Evaluating cost-effectiveness in the management of neuroendocrine neoplasms

White

Mújica-Mota

Snowsill

et al. 2020

Rev Endocr Metab Disord

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“…Thirdly, in view of increasing treatment options, cost-effectiveness is an important aspect to consider. Some initial attempts comparing everolimus, 177 Lu PRRT and sunitinib in advanced, unresectable, or metastatic progressive NETs have been reported [153]. However, information coming from such studies has to be interpreted carefully and its implementation into clinical practice may be challenging.…”

Section: Ongoing Challengesmentioning

confidence: 99%

Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs)

Megdanova-Chipeva

Lamarca

Backen

et al. 2020

Cancers

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Pancreatic neuroendocrine tumours (PanNETs) are rare diseases and a good example of how research is not only feasible, but also of crucial importance in the scenario of rare tumours. Many clinical trials have been performed over the past two decades expanding therapeutic options for patients with advanced PanNETs. Adequate management relies on optimal selection of treatment, which may be challenging for clinicians due to the fact that multiple options of therapy are currently available. A number of therapies already exist, which are supported by data from phase III studies, including somatostatin analogues and targeted therapies (sunitinib and everolimus). In addition, chemotherapy remains an option, with temozolomide and capecitabine being one of the most popular doublets to use. Peptide receptor radionuclide therapy was successfully implemented in patients with well-differentiated gastro-entero-pancreatic neuroendocrine tumours, but with certain questions waiting to be solved for the management of PanNETs. Finally, the role of immunotherapy is still poorly understood. In this review, the data supporting current systemic treatment options for locally advanced or metastatic PanNETs are summarized. Strategies for treatment selection in patients with PanNETs based on patient, disease, or drug characteristics is provided, as well as a summary of current evidence on prognostic and predictive biomarkers. Future perspectives are discussed, focusing on current and forthcoming challenges and unmet needs of patients with these rare tumours.

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[177Lu]Lu-DOTA-TATE versus standard of care in adult patients with gastro-enteropancreatic neuroendocrine tumours (GEP-NETs): a cost-consequence analysis from an Italian hospital perspective

Spada

Campana

Laudicella

et al. 2021

Eur J Nucl Med Mol Imaging

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Purpose To assess and compare clinical outcomes and costs, to the Italian healthcare system, of three therapeutic options approved in the management of adult patients with gastro-enteropancreatic neuroendocrine tumours (GEP-NETs). Methods We compared the efficacy, safety, and costs of [177Lu]Lu-DOTA-TATE, everolimus (both originator and generic products), and sunitinib in patients with advanced GEP-NETs (NET G1 and G2) that had progressed following treatment with somatostatin analogs (SSAs). A cost-consequence model was developed and validated by a panel of clinical experts from three NET reference centres in Italy. The clinical outcomes included in the model were median progression-free survival and the incidence of grade 3 or 4 adverse events (AEs), as reported in pivotal clinical trials. The costs for acquisition and administration of each treatment, and of managing AEs, were calculated from the perspective of the Italian national health service. Treatment costs per progression-free month were calculated separately for patients with NETs of pancreatic (PanNETs; all three treatments) and gastrointestinal (GI-NETs; [177Lu]Lu-DOTA-TATE and everolimus only) origin. Results In patients with PanNETs, total costs per progression-free month were €2989 for [177Lu]Lu-DOTA-TATE, €4975 for originator everolimus, €3472 for generic everolimus, and €5337 for sunitinib. In patients with GI-NETs, total costs per progression-free month were €3189 for [177Lu]Lu-DOTA-TATE, €4990 for originator everolimus, and €3483 for generic everolimus. Conclusions [177Lu]Lu-DOTA-TATE was associated with lower costs per progression-free month versus relevant treatment options in patients with GI-NETs or PanNETs (NET G1–G2; progressed following SSA treatment), although acquisition and administration costs are higher. These findings provide further economic arguments in the overall context of treatment decision-making.

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Everolimus, lutetium-177 DOTATATE and sunitinib for advanced, unresectable or metastatic neuroendocrine tumours with disease progression: a systematic review and cost-effectiveness analysis

Abstract: The National Institute for Health Research Health Technology Assessment programme.

Cited by 22 publications

References 157 publications

Evaluating cost-effectiveness in the management of neuroendocrine neoplasms

Evaluating cost-effectiveness in the management of neuroendocrine neoplasms

Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs)

[177Lu]Lu-DOTA-TATE versus standard of care in adult patients with gastro-enteropancreatic neuroendocrine tumours (GEP-NETs): a cost-consequence analysis from an Italian hospital perspective

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