A prospective, multi-institutional phase II study of GW786034 (pazopanib) and depot octreotide (sandostatin LAR) in advanced low-grade neuroendocrine carcinoma (LGNEC).

4001 Background: Current treatments options for advanced LGNEC are limited. Vascular endothelial growth factor (VEGF) pathway inhibitors, including bevacizumab, sorafenib,and sunitinib have shown preliminary evidence of activity in NEC. Additionally, octreotide has cytostatic activity in NEC. Pazopanib is a selective, orally available, small molecule inhibitor of the VEGFR-1, -2, and -3, PDGF-α, PDGF-β, and c-kit tyrosine kinases. We performed a prospective study of pazopanib administered in combination with octreotide in pts with advanced LGNEC. Methods: Pts with either carcinoid (C) or pancreatic NET (PNET) on a stable dose of depot octreotide (LAR) for ≥ 2 months were enrolled at 2 institutions (MDACC, DFCI). Pts with prior VEGF pathway inhibitor treatment were excluded. Pts received pazopanib 800mg PO daily in combination with LAR at their prior dose level. A 2-cohort (C, PNET), 2-stage design was employed, with early stopping if no RECIST-defined response was observed among the first 20 evaluable pts enrolled per cohort. Pts were followed for tumor response, toxicity, and survival. Results: 52 patients enrolled and 51 treated (29 PNET, 22 C) between 4/07 - 7/09. 25 (18 PNET, 7 C) had prior therapy. 46 (26 PNET, 20 C) completed 12 weeks of therapy and undergone response evaluation. No responders in first stage of C cohort, so accrual was stopped at 20 patients. PNET response rate was 17% (5/30) by ITT. There were 5 PR (all were in PNET cohort), 32 SD, 9 PD. Progression free survival (PFS) rate at week 24 was 76% (80% PNET, 71% C). Median PFS times were 12.7 and 11.7 mos, for C and PNET patients, respectively. Optional functional CT (fCT) was used to monitor BF, BV, MTT, and PS in 16 patients; results will be updated. CTC G3/4 toxicities were relatively rare and included: anemia (1), neutropenia (3), hypertriglyceridemia (2), transaminitis (3), fatigue (3), hypertension (6), nausea (1), diarrhea (3), pain (1), rash (1), syncope (1), and confusion (1). Conclusions: Treatment with pazopanib and octreotide is feasible and associated with tumor regression in pts with PNET. Encouraging PFS durations in both C and PNET pts were observed. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis