429O - A phase II trial of palbociclib in metastatic grade 1/2 pancreatic neuroendocrine tumors: the PALBONET study on behalf of the Spanish Taskforce Gro...

Date 10 September 2017
Event ESMO 2017 Congress
Session Endocrine and neuroendocrine tumours
Topics Anti-Cancer Agents & Biologic Therapy
Neuroendocrine Cancers
Endocrine Cancers
Presenter Enrique Grande Pulido
Citation Annals of Oncology (2017) 28 (suppl_5): v142-v157. 10.1093/annonc/mdx368
Authors E. Grande Pulido1, A. Teule2, T. Alonso-Gordoa1, P. Jiménez-Fonseca3, M. Benavent4, J. Capdevila5, A. Custodio6, R. Vera7, J. Munarriz8, A. La Casta-Muñoa9, R. Garcia-Carbonero10
  • 1Medical Oncology, Hospital Universitario Ramon y Cajal, 28031 - Madrid/ES
  • 2Medical Oncology, ICO Belvitge, 08026 - Barcelona/ES
  • 3Medical Oncology, H. U. Central de Asturias, 33011 - Oviedo/ES
  • 4Medical Oncology, H. U. Virgen del Rpcío, 41013 - Sevilla/ES
  • 5Gastrointestinal And Endocrine Tumor Unit, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 6Medical Oncology, Hospital Universitario la Paz, 28046 - Madrid/ES
  • 7Medical Oncology, Hospital de Navarra, 31008 - Pamplona/ES
  • 8Medical Oncology, Hospital General de Castellón, 12004 - Castellón/ES
  • 9Medical Oncology, H. U. Donostia, 20014 - San Sebastian/ES
  • 10Medical Oncology Department, University Hospital 12 De Octubre, 28041 - Madrid/ES

Abstract

Background

Overexpression or amplification of cell cycle regulators like cyclin-dependent kinase-4 (Cdk-4), phospho-Rb1, or cyclin D1 are observed in 58%, 68%, and 68% pancreatic neuroendocrine tumors (pNETs), respectively. Moreover, these alterations correlate with a more aggressive behavior. Palbociclib targets Cdk-4/6 and has shown in vitro activity in pNETs cell lines overexpressing Cdk-4.

Methods

In this non-randomized, open-label, phase II study, patients (pts) with metastatic grade (G) 1/2 pNETs were recruited from 10 centres belonging to the Spanish Taskforce Group of NETS (GETNE). Palbociclib 125 mg was given once daily for 21 of 28 days until disease progression (DP) or unacceptable toxicity. The initial planned recruitment was 21 patients based on a 2-stage Simon’s phase II design, where palbociclib would be considered inactive if 

Results

21 pts were included. One pt withdrew from the study due to clinical deterioration after < 1 month (m). 54% were males, mean age was 54 years (range: 33-66), and 67% had received > 3 previous lines of therapy (23.8% pazopanib; 80.9% sunitinib; 47.6% everolimus) beside somatostatin analogs. 20 pts were evaluable for ORR with a median follow up of 10m (4.23-12.43). No responses (0%) were observed; 11 (55%) pts had stable disease and 6 of them lasted more than 6m; 7 (35%) pts had progression as best response. 1 pt had tumor shrinkage of 8%. Median PFS was 1.9m (IC95% 0 - 13). Median OS was 16.6m (IC95% 9.3 – 23.9). Most frequent toxicities of any grade were: asthenia (16.2%), diarrhea (6.4%), abdominal pain (4.7%), nausea (4.3%) and neutropenia (11.5%). 5 pts developed G3-4 neutropenia (1 case of febrile neutropenia) and 2 pts G3-4 thrombocitopenia.

Conclusions

Lack of activity was observed with palbociclib in 21 molecularly unselected and heavily pretreated patients with advanced G1/2 pNETs. Translational studies correlating activity with molecular tumor markers and Ki67 proliferation index are ongoing.

Clinical trial identification

EudraCT: 2014-003924-34

Legal entity responsible for the study

GETNE (Spanish Taskforce Group for Neuroendorine Tumors)

Funding

Pfizer

Disclosure

E. Grande Pulido: Advisor for Ipsen, Pfizer, Lexicon. Scientific lectures for Pfizer and Ipsen. All other authors have declared no conflicts of interest.