Background: The Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors (CLARINET) trial showed prolonged progression-free survival in patients initially treated with lanreotide versus placebo. We evaluated the cost-effectiveness of upfront lanreotide versus active surveillance with lanreotide administered after progression in patients with metastatic enteropancreatic neuroendocrine tumors (NETs), both of which are treatment options recommended in NCCN Clinical Practice Guidelines in Oncology for Neuroendocrine and Adrenal Tumors. Methods: We developed a Markov model calibrated to the CLARINET trial and its extension. We based the active surveillance strategy on the CLARINET placebo arm. We calculated incremental cost-effectiveness ratios (ICERs) in dollars per quality-adjusted life-year (QALY). We modeled lanreotide’s cost at $7,638 per 120 mg (average sales price plus 6%), used published utilities (stable disease, 0.77; progressed disease, 0.61), adopted a healthcare sector perspective and lifetime time horizon, and discounted costs and benefits at 3% annually. We examined sensitivity to survival extrapolation and modeled octreotide long-acting release (LAR) ($6,183 per 30 mg). We conducted one-way, multiway, and probabilistic sensitivity analyses. Results: Upfront lanreotide led to 5.21 QALYs and a cost of $804,600. Active surveillance followed by lanreotide after progression led to 4.84 QALYs and a cost of $590,200, giving an ICER of $578,500/QALY gained. Reducing lanreotide’s price by 95% (to $370) or 85% (to $1,128) per 120 mg would allow upfront lanreotide to reach ICERs of $100,000/QALY or $150,000/QALY. Across a range of survival curve extrapolation scenarios, pricing lanreotide at $370 to $4,000 or $1,130 to $5,600 per 120 mg would reach ICERs of $100,000/QALY or $150,000/QALY, respectively. Our findings were robust to extensive sensitivity analyses. The ICER modeling octreotide LAR is $482,700/QALY gained. Conclusions: At its current price, lanreotide is not cost-effective as initial therapy for patients with metastatic enteropancreatic NETs and should be reserved for postprogression treatment. To be cost-effective as initial therapy, the price of lanreotide would need to be lowered by 48% to 95% or 27% to 86% to reach ICERs of $100,000/QALY or $150,00/QALY, respectively.
Submitted October 31, 2019; accepted for publication March 23, 2020.
Previous presentation: This study was presented as an abstract and poster at the North American Neuroendocrine Tumor Society (NANETS) Annual Multidisciplinary NET Disease Symposium; October 6, 2018; Seattle, Washington. Abstract 114.
Author contributions:Study concept and design: All authors. Data collection and assembly: Barnes, Lin, Gupta, Kunz. Data analysis and interpretation: Barnes, Lin, Owens, Goldhaber-Fiebert, Kunz. Manuscript preparation: All authors.
Disclosures: Dr. Kunz has disclosed that she receives grant/research support from Advanced Accelerator Applications, Ipsen, Lexicon, Xencor, and B.R.A.H.M.S., and that she is a scientific advisor for Advanced Accelerator Applications. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.
Funding: Drs. Barnes and Lin were supported by funding from the Office of Academic Affiliations, Department of Veterans Affairs, Advanced Fellowship in HSR&D. Dr. Owens was supported by the Department of Veterans Affairs. All views expressed in this article are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs.
Correspondence: James I. Barnes, MD, MS, Center for Primary Care and Outcomes Research/Center for Health Policy, Department of Medicine, Stanford University School of Medicine, 117 Encina Commons, Stanford, CA 94305. Email: firstname.lastname@example.org
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