The PALBONET Trial: A Phase II Study of Palbociclib in Metastatic Grade 1 and 2 Pancreatic Neuroendocrine Tumors (GETNE-1407).

Abstract

LESSONS LEARNED:

Palbociclib demonstrated no detectable activity in molecularly unselected and heavily pretreated patients with advanced grade 1/2 pancreatic neuroendocrine tumors. Predictive biomarkers that improve patient selection should be investigated in future studies of palbociclib.

BACKGROUND:

Palbociclib, a CDK4/6 inhibitor, has shown in vitro activity in pancreatic neuroendocrine tumor (pNET) cell lines. Here we prospectively assessed the activity and safety of palbociclib in monotherapy in metastatic refractory pNETs.

METHODS:

This was a nonrandomized, open-label, phase II study of patients with metastatic grade (G)1/2 pNETs recruited from 10 centers in Spain. Palbociclib 125 mg was orally administered once daily for 21 of 28 days until disease progression or unacceptable toxicity.

RESULTS:

Twenty-one patients were included; 52.4% were men, and median age was 57.4 years (range, 37.4-73.4). Patients had previously received a median of three prior lines of systemic therapy (range, 1-10) for advanced disease (somatostatin analogues, 71.4%; sunitinib, 81.0%; everolimus, 47.6%; chemotherapy, 47.6%). Nineteen patients were evaluated for objective response rate (ORR), with a median follow-up of 12.4 months (range, 7.53-19.33). No objective and confirmed responses were observed (0%); 11 (57.9%) patients had stable disease, and 6 of them lasted more than 6 months; 8 (42.1%) patients had disease progression as best response. Median progression-free survival (PFS) was 2.6 months (95% confidence interval [CI], 0-14.4) and median overall survival (OS) was 18.7 months (95% CI, 7.4-29.9; Fig. 1). Most frequent toxicities of any grade were asthenia (76.2%), neutropenia (42.9%), diarrhea (33.3%), and nausea (33.3%). Five (23.8%) patients developed G3-4 neutropenia and two (9.5%) patients developed G3-4 thrombocytopenia.

CONCLUSION:

Lack of activity was observed with palbociclib as a single agent in molecularly unselected and heavily pretreated patients with advanced G1/2 pNETs.

• Authors: Enrique Grande, Alex Teulé, Teresa Alonso-Gordoa, Paula Jiménez-Fonseca, Marta Benavent, Jaume Capdevila, Ana Custodio, Ruth Vera, Javier Munarriz, Adelaida La Casta, Juan José Díez, Pablo Gajate, Javier Molina-Cerrillo, Ignacio Matos, Eva María Cristóbal, José C Ruffinelli, José Palacios, Rocío García-Carbonero
• Journal: The oncologist (Oncologist) Vol. 25 Issue 9 Pg. 745-e1265 (09 2020) ISSN: 1549-490X [Electronic] England
• PMID: 32045050 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © AlphaMed Press; the data published online to support this summary are the property of the authors.

Chemical References

• Piperazines
• Pyridines
• palbociclib

Topics

• Antineoplastic Combined Chemotherapy Protocols
• Female
• Humans
• Male
• Middle Aged
• Neuroendocrine Tumors (drug therapy)
• Pancreatic Neoplasms (drug therapy)
• Piperazines (adverse effects)
• Pyridines
• Spain