PAZONET: Results of a phase II trial of pazopanib as a sequencing treatment in progressive metastatic neuroendocrine tumors (NETs) patients (pts), on behalf of the Spanish task force for NETs (GETNE)—NCT01280201.

Abstract

4119 Background: Pazopanib is an oral tyrosine kinase inhibitor of the VEGFR, PDGFR and KIT that has demonstrated clinical activity in NETs. The aims of our study were to assess efficacy, safety and potential predictive biomarkers of pazopanib in pts with NETs who had previously failed to at least one antiangiogenic or mTOR inhibitor treatment. Methods: Pts presented locally-advanced or metastatic gastrointestinal or pancreatic NET disease documented as progressive. Pazopanib 800 mg was given daily until disease progression (DP) or unacceptable toxicity. Primary endpoint was Clinical Benefit Rate (CBR) defined as Complete Response plus Partial Response (PR) plus Stable Disease (SD) at 6 months by RECIST-V-1.0. Optimal two-stage Simon design was utilized with H1 and H0 set at 70 % and 50 % respectively, Kaplan-Meier estimates waere used for the analysis of time-to-event variables: 95% CI. Results: 33 pts were evaluable for response per protocol. 54.5% males, mean age 60.7±10.3 years. At 6 months, 2 pts had PR (6%), 26 SD (79%), and 5 DP (15%), thus the CBR was 85%. By subgroups, CBR was 100% in pts with no previous targeted therapy (7 pts), 89% in pts with previous mTOR inhibitors (9 pts), 83% in pts with previous antiangiogenics (12 pts), and 60% in pts with previous antiangiogenics and mTOR inhibitors (5 pts). The sum of the longest diameter of target lesions had a decrease over 10% in 22% of pts (29% without previous biological treatment, 22% mTOR without prior multitarget, 18% prior multitarget without mTor, and 20% with previous multitarget and mTOR. Median PFS was only reached in the subgroup of pts (26 pts) with previously treated with antiangiogenics and mTOR inhibitors (20.6 weeks, 95% CI, 10.4-30.8). Most frequent toxicities, any grade: asthenia (75%), diarrhoea (63%), nausea (42%). Translational studies on angiogenesis and inmunohistochemistry biomarkers and CTCs are ongoing. Conclusions: Pazopanib at 800 mg daily has promising activity in advanced NET regardless of previous treatment with other targeted therapies. This trial may introduce the concept of treatment sequencing with novel targeted agents in NETs.