Pazopanib in pretreated advanced neuroendocrine tumors: a phase II, open-label trial of the Spanish Task Force Group for Neuroendocrine Tumors (GETNE)
E Grande, J Capdevila, D Castellano, A Teulé, I Durán, J Fuster, I Sevilla, P Escudero, J Sastre, J García-Donas, O Casanovas, J Earl, L Ortega, M Apellaniz-Ruiz, C Rodriguez-Antona, T Alonso-Gordoa, J J Díez, A Carrato, R García-Carbonero, E Grande, J Capdevila, D Castellano, A Teulé, I Durán, J Fuster, I Sevilla, P Escudero, J Sastre, J García-Donas, O Casanovas, J Earl, L Ortega, M Apellaniz-Ruiz, C Rodriguez-Antona, T Alonso-Gordoa, J J Díez, A Carrato, R García-Carbonero
Abstract
Background: The management of advanced neuroendocrine tumors (NETs) has recently changed. We assessed the activity of pazopanib after failure of other systemic treatments in advanced NETs.
Methods: This was a multicenter, open-label, phase II study evaluating pazopanib as a single agent in advanced NETs (PAZONET study). The clinical benefit rate (CBR) at 6 months was the primary end point. Translational correlation of radiological response and progression-free survival (PFS) with circulating and tissue biomarkers was also evaluated.
Results: A total of 44 patients were enrolled. Twenty-five patients (59.5%) were progression-free at 6 months (4 partial responses, 21 stable diseases) with a median PFS of 9.5 months [95% confidence interval (CI) 4.8-14.1]. The CBR varied according to prior therapy received, with 73%, 60% and 25% in patients treated with prior multitarget inhibitors, prior mTOR inhibitors and both agents, respectively. A nonsignificant increase in PFS was observed in patients presenting lower baseline circulating tumor cell (CTC) counts (9.1 versus 5.8 months; P = 0.22) and in those with decreased levels of soluble-vascular endothelial growth factor receptor-2 (sVEGFR-2) (12.6 versus 9.1 months; P = 0.067). A trend toward reduced survival was documented in patients with VEGFR3 rs307821 and rs307826 missense polymorphisms [hazard ratio (HR): 12.3; 95% CI 1.09-139.2; P = 0.042 and HR: 6.9; 95% CI 0.96-49.9; P = 0.055, respectively].
Conclusions: Pazopanib showed clinical activity in patients with advanced NETs regardless of previous treatments. Additionally, CTCs, soluble-s VEFGR-2 and VEGFR3 gene polymorphisms constitute potential biomarkers for selecting patients for pazopanib (NCT01280201).
Clinical trial number: NCT01280201.
Keywords: angiogenic markers; bronchial carcinoids; gastroenteropancreatic tumors; pazopanib; polymorphisms; thymic tumors.
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Source: PubMed