1157O - PAZONET: a phase II trial of pazopanib as a sequencing treatment in progressive metastatic neuroendocrine tumors (NETs) patients (pts), on behalf of...

Date 29 September 2012
Event ESMO Congress 2012
Session NETs and endocrine tumors
Topics Anticancer agents
Neuroendocrine Tumours
Biological Therapy
Presenter Enrique Grande
Authors E. Grande1, D.E. Castellano2, R. Garcia-Carbonero3, A. Teule4, I. Duran5, J. Fuster6, I. Sevilla7, P. Escudero8, J. Sastre9
  • 1Ramon y Cajal University Hospital, 28034 - Madrid/ES
  • 2Medical Oncology, Hospital Universitario 12 de Octubre, Madrid/ES
  • 3Oncology Department, Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES
  • 4Medical Oncology, Institut Català d'Oncologia L'Hospitalet, Barcelona/ES
  • 5Departamento De Oncologia, Hospital Madrid Norte San ChinarroCentro Integral Oncologico Clara Campal, ES-28050 - Madrid/ES
  • 6Medical Oncology, Hospital Son Espases, Palma de Mallorca/ES
  • 7Medical Oncology, Virgen de la Victoria University Hospital, Malaga/ES
  • 8Medical Oncology, Hospital Universitario Lozano Blesa, Zaragoza/ES
  • 9Medical Oncology, Hospital Clinico San Carlos, Madrid/ES



Pazopanib is an oral tyrosine kinase inhibitor of the VEGFR, PDGFR and KIT with demonstrated clinical activity in NETs. The aims of our study were to assess efficacy, safety and potential predictive biomarkers of pazopanib in pts with NETs who may have received previous antiangiogenic or mTOR inhibitor treatment.


All pts had pancreatic or extra-pancreatic metastatic NET disease documented as progressive. Pazopanib 800 mg was given daily until disease progression (DP) or unacceptable toxicity. Primary endpoint was Clinical Benefit Rate (CBR) at 6 months (m) defined as Complete Response (CR) plus Partial Response (PR) plus Stable Disease (SD) by RECIST-V-1.0. Optimal two-stage Simon design was utilized with H1 and H0 set at 70 % and 50 % respectively, Kaplan-Meier estimates were used for the analysis of time-to-event variables: 95% CI.


41 evaluable pts for response per protocol. 53.7% males, mean age 59.2 ± 10.3 years. At 6 months, 3 pts had PR (7.36%), 32 SD (78.0%), and 6 DP (14.6%), thus the CBR was 85.4%. Global median PFS 48,3 (13.9-82.7) weeks (w). By subgroups, CBR at 6 m and median PFS were 100% and 25.7 w in pts with no previous targeted therapy (9 pts), 88.9% and 48.3 w in pts with previous mTOR inhibitors (9 pts), 83.3% and 50.3 w in pts with previous antiangiogenics (16 pts) and 71.4% and 20.6 w in pts with previous antiangiogenics and mTOR inhibitors (7 pts) respectively. The sum of the longest diameter of target lesions had a decrease > 10% in 32.5 % of pts (37.5% without previous biological treatment, 22.2 % with previous mTOR inhibitor, 31.3% with prior multitarget inhibitor, and 42.9% with previous multitarget and mTOR, p = 0.506). Most frequent toxicities at of any grade were: asthenia (75%), diarrhoea (63%), nausea (42%). Translational studies on angiogenesis and inmunohistochemistry biomarkers and CTCs are ongoing.


Pazopanib 800 mg daily has promising activity in advanced NET regardless of previous treatment with other targeted therapies. This trial suggests the role that treatment sequencing with novel targeted agents may have in NETs.


All authors have declared no conflicts of interest.