title: Evaluation of the efficacy and safety of lanreotide in combination with targeted therapies in patients with neuroendocrine tumours in clinical practice: a retrospective cross-sectional analysis.
abstract: BACKGROUND
  Based on the mechanism of action, combining somatostatin analogues (SSAs) with mTOR inhibitors or antiangiogenic agents may provide synergistic effects for the treatment of patients with neuroendocrine tumours (NETs). Herein, we investigate the use of these treatment combinations in clinical practice.
  
  
  METHODS
  This retrospective cross-sectional analysis of patients with NETs treated with the SSA lanreotide and targeted therapies at 35 Spanish hospitals evaluated the efficacy and safety of lanreotide treatment combinations in clinical practice. The data of 159 treatment combinations with lanreotide in 133 patients was retrospectively collected.
  
  
  RESULTS
  Of the 133 patients, with a median age of 59.4 (16-83) years, 70 (52.6%) patients were male, 64 (48.1%) had pancreatic NET, 23 (17.3%) had ECOG PS ≥ 2, 41 (30.8%) had functioning tumours, 63 (47.7%) underwent surgery of the primary tumour, 45 (33.8%) had received prior chemotherapy, and 115 (86.5%) had received prior SSAs. 115 patients received 1 lanreotide treatment combination and 18 patients received between 2 and 5 combinations. Lanreotide was mainly administered in combination with everolimus (73 combinations) or sunitinib (61 combinations). The probability of being progression-free was 78.5% (6 months), 68.6% (12 months) and 57.0% (18 months) for patients who only received everolimus plus lanreotide (n = 57) and 89.3% (6 months), 73.0% (12 months), and 67.4% (18 months) for patients who only received sunitinib and lanreotide (n = 50). In patients who only received everolimus plus lanreotide the median time-to-progression from the initiation of lanreotide combination treatment was 25.8 months (95% CI, 11.3, 40.3) and it had not yet been reached among the subgroup of patients only receiving sunitinib plus lanreotide. The safety profile of the combination treatment was comparable to that of the targeted agent alone.
  
  
  CONCLUSIONS
  The combination of lanreotide and targeted therapies, mainly everolimus and sunitinib, is widely used in clinical practice without unexpected toxicities and suggests efficacy that should be explored in randomized prospective clinical trials.
authors.affiliation: Medical Oncology Department, Vall d'Hebron University Hospital, Autonomous University of Barcelona, P. Vall d'Hebron 119-129, 08035, Barcelona, Spain. jacapdevila@vhebron.net.
authors.forename: Jaume
authors.initials: J
authors.lastname: Capdevila
authors.affiliation: Medical Oncology Department, Virgen de la Victoria University Hospital , Campus Universitario Teatinos, 29010, Málaga, Spain. isevilla02@yahoo.es.
authors.forename: Isabel
authors.initials: I
authors.lastname: Sevilla
authors.affiliation: Medical Oncology Department, Miguel Servet University Hospital, Paseo Isabel la Católica, 1-3, 50009, Zaragoza, Spain. alonord@gmail.com.
authors.forename: Vicente
authors.initials: V
authors.lastname: Alonso
authors.affiliation: Medical Oncology Department, University Hospital Complex, As Xubias, 84, 15006, A Coruña, Spain. luis.anton.aparicio@sergas.es.
authors.forename: Luís
authors.initials: L
authors.lastname: Antón Aparicio
authors.affiliation: Medical Oncology Department, Asturias Central University Hospital, Calle Celestino Villamil, 33006, Oviedo, Spain. palucaji@hotmail.com.
authors.forename: Paula
authors.initials: P
authors.lastname: Jiménez Fonseca
authors.affiliation: Medical Oncology Department, Ramón y Cajal University Hospital, Ctra. de Colmenar Viejo, km. 9100, 28034, Madrid, Spain. egrande@oncologiahrc.com.
authors.forename: Enrique
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authors.lastname: Grande
authors.affiliation: Medical Oncology Department, Virgen Macarena University Hospital, Avda Dr Fedriani, 3 41009, Sevilla, Spain. juanjoreinaz@yahoo.es.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Reina
authors.affiliation: Medical Oncology Department, Catalan Oncology Institute (ICO-Badalona), Germans Trias i Pujol University Hospital, Carretera Canyet s/n, Badalona, 08016, Barcelona, Spain. jmanzano@iconcologia.net.
authors.forename: José Luís
authors.initials: JL
authors.lastname: Manzano
authors.affiliation: Medical Oncology Department, Virgen de la Arrixaca University Hospital, Ctra. Madrid Cartagena, 30120, Murcia, Spain. juand.alonso@carm.es.
authors.forename: Juan Domingo
authors.initials: JD
authors.lastname: Alonso Lájara
authors.affiliation: Medical Oncology Department, La Paz University Hospital, Paseo de la Castellana 261, 28046, Madrid, Spain. jorge.barriuso@salud.madrid.org.
authors.forename: Jorge
authors.initials: J
authors.lastname: Barriuso
authors.affiliation: Medical Oncology Department, 12 de Octubre University Hospital, Avda. de Córdoba, 28041, Madrid, Spain. cdanicas@hotmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Castellano
authors.affiliation: Medical Oncology Department, Toledo Hospital Complex, Av de Barber 30, 45071, Toledo, Spain. boladiez39@yahoo.es.
authors.forename: Javier
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authors.lastname: Medina
authors.affiliation: Medical Oncology Department, Marqués de Valdecilla University Hospital, Av Valdecilla, 39008, Santander, Spain. clopez@humv.es.
authors.forename: Carlos
authors.initials: C
authors.lastname: López
authors.affiliation: Medical Oncology Department, La Fe University Hospital, Avinguda de Campanar 21, 46026, Valencia, Spain. segura_ang@gva.es.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Segura
authors.affiliation: Medical Oncology Department, Cruces University Hospital, Plaza Cruces, 48903, Barakaldo, Vizcaya, Spain. sergio.carrerarevilla@osakidetza.net.
authors.forename: Sergio
authors.initials: S
authors.lastname: Carrera
authors.affiliation: Medical Oncology Department, Burgos University Hospital, Avda. Islas Baleares 3, 09006, Burgos, Spain. gcrespoherrero@hotmail.com.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Crespo
authors.affiliation: Medical Oncology Department, Son Dureta University Hospital, C/ Andrea Doria 55, 07014, Palma de Mallorca, Spain. jose.fuster@ssib.es.
authors.forename: José
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authors.lastname: Fuster
authors.affiliation: Medical Oncology Department, Castellón Provincial Hospital Consortium, Av Doctor Clara 19, 12002, Castellón de la Plana, Spain. jmunarriz@comcas.es.
authors.forename: Javier
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authors.lastname: Munarriz
authors.affiliation: Medical Oncology Department, Gregorio Marañon Hospital, Calle Doctor Esquerdo 46, 28007, Madrid, Spain. pgarcaalfonso@gmail.com.
authors.forename: Pilar
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mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000401:mortality; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D012189:Retrospective Studies; D013004:Somatostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin