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Anti-tumour activity of everolimus and sunitinib in neuroendocrine neoplasms
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Univ Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece.ORCID iD: 0000-0003-4224-8912
Univ Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece.
Univ Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece.
Univ Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece;Univ Athens, Med Sch, Dept Biol Chem, Athens, Greece.
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2019 (English)In: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 8, no 6, p. 641-653Article in journal (Refereed) Published
Abstract [en]

Comparisons between everolimus and sunitinib regarding their efficacy and safety in neuroendocrine neoplasms (NENs) are scarce. We retrospectively analysed the clinicopathological characteristics and outcomes in 92 patients with well-differentiated (WD) NEN of different origin (57 pancreatic NENs (PanNENs)), treated with molecular targeted therapy (MTT) with everolimus or sunitinib, first- (73: 19) or second-line (sequential; 12: 22) for progressive disease. Disease control rates (DCR: partial response or stable disease) at first-line were higher in all patients treated with everolimus than sunitinib (64/73 vs 12/19, P = 0.012). In PanNENs, DCR at first-line everolimus was 36/42 versus 9/15 with sunitinib (P = 0.062). Progression-free survival (PFS) at first-line everolimus was longer than sunitinib (31 months (95% CI: 23.1-38.9) vs 9 months (95% CI: 0-18.5); log-rank P < 0.0001) in the whole cohort and the subset of PanNENs (log-rank P < 0.0001). Median PFS at second-line MTT was 12 months with everolimus (95% CI: 4.1-19.9) vs 13 months with sunitinib (95% CI: 9.3-16.7; log-rank P = 0.951). Treatment with sunitinib (HR: 3.47; 95% CI: 1.5-8.3; P value: 0.005), KI67 > 20% (HR: 6.38; 95% CI: 1.3-31.3; P = 0.022) and prior chemotherapy (HR: 2.71; 95% CI: 1.2-6.3; P = 0.021) were negative predictors for PFS at first line in multivariable and also confirmed at multi-state modelling analyses. Side effect (SE) analysis indicated events of serious toxicities (Grades 3 and 4: n = 13/85 for everolimus and n = 4/41 for sunitinib). Discontinuation rate due to SEs was 20/85 for everolimus versus 4/41 for sunitinib (P = 0.065). No additive toxicity of second-line MTT was confirmed. Based on these findings, and until reliable predictors of response become available, everolimus may be preferable to sunitinib when initiating MTT in progressive NENs.

Place, publisher, year, edition, pages
Bioscientifica, 2019. Vol. 8, no 6, p. 641-653
Keywords [en]
neuroendocrine neoplasms, molecular targeted therapy, everolimus, sunitinib
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-390599DOI: 10.1530/EC-19-0134ISI: 000472586000004PubMedID: 31026812OAI: oai:DiVA.org:uu-390599DiVA, id: diva2:1342272
Funder
Swedish Society of MedicineAvailable from: 2019-08-13 Created: 2019-08-13 Last updated: 2019-08-13Bibliographically approved

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