1156O - RAMSETE: a single-arm, multicenter, single-stage phase II trial of RAD001 (everolimus) in advanced and metastatic silent neuro-endocrine tumours in...

Date 29 September 2012
Event ESMO Congress 2012
Session NETs and endocrine tumors
Topics Cytotoxic agents
Neuroendocrine Cancers
Biological therapy
Presenter Marianne Pavel
Authors M. Pavel1, B. Wiedenmann2, J. Capdevila3, J.W. Valle4, W.W. De Herder5, C. Metzer6, R. Salazar7, D. Horsch8, K. Oberg9
  • 1Dept Of Gastroenterology & Hepatology, Charité Universitätsmedizin Berlin, 13353 - Berlin/DE
  • 2Medizinische Klinik, Charité Universitätsmedizin Berlin, 13353 - Berlin/DE
  • 3Medical Oncology, Hospital Vall d'Hebrón, Barcelona/ES
  • 4Medical Oncology, The Christie NHS Foundation Trust, GB-M20 4BX - Manchester/UK
  • 5Endocrine Oncology, Erasmus University Medical Center, Rotterdam/NL
  • 6Internal Medicine And Clinical Chemistry, Ruprecht-Karls-Universitat Heidelberg Medizinische Klinik und Poliklinik, Heidelberg/DE
  • 7Medical Oncology, ICO Hospital Duran i Reynals, Barcelona/ES
  • 8Gastroenterology And Endocrinology, ChA Klinik für Innere Medizin, Bad Berka/DE
  • 9Endocrine Oncology Unit, Dept Of Medicine, Uppsala University, Uppsala/SE




Everolimus is an oral inhibitor of the mammalian target of rapamycin and approved for treatment of advanced pancreatic neuroendocrine tumors (pNET). Its efficacy in nonsyndromic, nonpancreatic NET is unknown. Here we report a secondary exploratory post hoc analysis by tumor origin of the RAMSETE trial.


RAMSETE include patients (pts) with advanced, progressive, nonsyndromic, nonpancreatic NET who received everolimus (10 mg/day) monotherapy. Primary endpoint was objective response rate (per RECIST v1.0) by central radiologic review. Secondary endpoints included progression-free survival (PFS).


Database lock was Dec 1, 2011, and included 73 pts with median everolimus treatment of 193 days. In the total population, the best response was stable disease (55%) with a median PFS of 185 days (95% CI: 158-255). 22 (30.1%) pts had primary tumor origin in the lung, thymus, bronchus, or mediastinum; 34 (46.6%) pts had primary tumor origin other than the lung, bronchus, or mediastinum (the largest subsets included small bowel/ileum [n = 16], rectum [n = 4], and caecum [n = 2]); and 17 (23.3%) pts had unknown primary tumor origin. Tumor characteristics and efficacy by tumor origin site are detailed in the Table. Everolimus was associated with a high proportion of stable disease along with a favorable PFS in pts with nonsydromic, nonpancreatic NET.


These results provide evidence that everolimus may be effective in nonsyndromic, nonpancreatic NET with diverse tumor origin sites and in pts with high tumor grade. These data support previous results from phase III trials that indicate everolimus is effective in pancreatic NET (RADIANT-3) and in NET associated with carcinoid syndrome (RADIANT-2).

Characteristic and Endpoint Lung, thymic, bronchial, mediastinal (n = 22) Other than lung (n = 34) Unknown (n = 17)
Well differentiated, % 40.9 97.0 82.3
Moderately differentiated, % 59.0 2.9 17.6
Ki67 >10%, % 62.5 42.8 50.0
Stable disease, % 63.2 42.9 69.2
Progressive disease, % 36.8 57.1 30.8
Median PFS, days (95% CI) 189 (84–321) 174 (118–245) 316 (126–337)


M. Pavel: Honoraria for presentations and participation in advisory board meetings for Novartis, Ipsen, Pfizer; Research grant from Novartis.

B. Wiedenmann: Honoraria from and consultancy with Novartis, Ipsen, Pfizer, and Lexicon.

J.W. Valle: Consultant/advisory relationship with Novartis; Honoraria from Novartis.

W.W. De Herder: Consultant/advisory relationship with Novartis; Honoraria from Novartis.

R. Salazar: Research funding from Novartis; Honoraria from Novartis.

D. Horsch: Consultant or advisory role with Pfizer, Novartis, and IPSEN; honoraria from Pfizer and Novartis; research funding from Novartis, Ipsen, MDS, Nordion, Covidien, Eckart and Ziegler.

K. Oberg: Consultant/advisory relationship with Novartis; Honoraria from Novartis.

All other authors have declared no conflicts of interest.