title: Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study.
abstract: In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1/2 (Ki-67 ≤ 10%) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg (n = 101) or placebo (n = 103) for 96 weeks or until death/progressive disease (PD) in CLARINET study. Patients with stable disease (SD) at core study end (lanreotide/placebo) or PD (placebo only) continued or switched to lanreotide in the OLE. In total, 88 patients (previously: lanreotide, n = 41; placebo, n = 47) participated: 38% had pancreatic, 39% midgut and 23% other/unknown primary tumours. Patients continuing lanreotide reported fewer adverse events (AEs) (all and treatment-related) during OLE than core study. Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies, except more diarrhoea was considered treatment-related in OLE (overall diarrhoea unchanged). Median lanreotide PFS (core study randomisation to PD in core/OLE; n=101) was 32.8 months (95% CI: 30.9, 68.0). A sensitivity analysis, addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE (n=13) had PD 24 weeks after last core assessment, found median PFS remaining consistent: 30.8 months (95% CI: 30.0, 31.3). Median time to further PD after placebo-to-lanreotide switch (n=32) was 14.0 months (10.1; not reached). This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability. CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs.
authors.affiliation: Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France m.caplin@ucl.ac.uk.
authors.forename: Martyn E
authors.initials: ME
authors.lastname: Caplin
authors.affiliation: Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Pavel
authors.affiliation: Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France.
authors.forename: Jarosław B
authors.initials: JB
authors.lastname: Ćwikła
authors.affiliation: Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France.
authors.forename: Alexandria T
authors.initials: AT
authors.lastname: Phan
authors.affiliation: Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France.
authors.forename: Markus
authors.initials: M
authors.lastname: Raderer
authors.affiliation: Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Sedláčková
authors.affiliation: Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cadiot
authors.affiliation: Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Wolin
authors.affiliation: Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France.
authors.forename: Jaume
authors.initials: J
authors.lastname: Capdevila
authors.affiliation: Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France.
authors.forename: Lucy
authors.initials: L
authors.lastname: Wall
authors.affiliation: Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France.
authors.forename: Guido
authors.initials: G
authors.lastname: Rindi
authors.affiliation: Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France.
authors.forename: Alison
authors.initials: A
authors.lastname: Langley
authors.affiliation: Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Martinez
authors.affiliation: Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France.
authors.forename: Edda
authors.initials: E
authors.lastname: Gomez-Panzani
authors.affiliation: Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruszniewski
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D006801:Humans; D007414:Intestinal Neoplasms / Q000188:drug therapy*; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D010456:Peptides, Cyclic / Q000009:adverse effects / Q000627:therapeutic use*; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin
keywords: anti-tumour effects; lanreotide Autogel; neuroendocrine tumours; open-label extension