Grande, EnriqueTeulé, AlexAlonso-Gordoa, TeresaJiménez-Fonseca, PaulaBenavent, MartaCapdevila, JaumeCustodio, AnaVera, RuthMunarriz, JavierLa Casta, AdelaidaDíez, Juan JoséGajate, PabloMolina-Cerrillo, JavierMatos, IgnacioCristóbal, Eva MaríaRuffinelli, José CPalacios, JoséGarcía-Carbonero, Rocío2023-02-082023-02-082020-02-11http://hdl.handle.net/10668/15086Palbociclib 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. 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. 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. 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. Lack of activity was observed with palbociclib as a single agent in molecularly unselected and heavily pretreated patients with advanced G1/2 pNETs.enAntineoplastic Combined Chemotherapy ProtocolsFemaleHumansMaleMiddle AgedNeuroendocrine TumorsPancreatic NeoplasmsPiperazinesPyridinesSpainresearch article32045050open access10.1634/theoncologist.2020-00331549-490XPMC7485337https://onlinelibrary.wiley.com/doi/pdfdirect/10.1634/theoncologist.2020-0033https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485337/pdf