Anti-tumour activity of everolimus and sunitinib in neuroendocrine neoplasms

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Daskalakis, KosmasUppsala universitet,Endokrinkirurgi,Univ Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece (author)

Anti-tumour activity of everolimus and sunitinib in neuroendocrine neoplasms

Article/chapterEnglish2019

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Bioscientifica,2019
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LIBRIS-ID:oai:DiVA.org:uu-390599
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-390599URI
https://doi.org/10.1530/EC-19-0134DOI

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Language:English
Summary in:English

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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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
neuroendocrine neoplasms
molecular targeted therapy
everolimus
sunitinib

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Tsoli, MarinaUniv Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece (author)
Angelousi, AnnaUniv Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece (author)
Kassi, EvanthiaUniv Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece;Univ Athens, Med Sch, Dept Biol Chem, Athens, Greece (author)
Alexandraki, Krystallenia, IUniv Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece (author)
Kolomodi, DeniseUniv Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece (author)
Kaltsas, GregoryUniv Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece;Univ Warwick, Univ Hosp, Warwick Med Sch, Clin Sci Res Labs, Coventry, W Midlands, England;Coventry Univ, Fac Hlth & Life Sci, Ctr Appl Biol & Exercise Sci, Coventry, W Midlands, England (author)
Koumarianou, AnnaUniv Athens, Haematol Oncol Unit, Dept Internal Med 4, Attikon Univ Gen Hosp, Athens, Greece (author)
Uppsala universitetEndokrinkirurgi (creator_code:org_t)

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In:Endocrine Connections: Bioscientifica8:6, s. 641-6532049-3614

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