Phase 1b study of pasireotide, everolimus, and selective internal radioembolization therapy for unresectable neuroendocrine tumors with hepatic metastases. Issue 9 (16th February 2018)

• Record Type: Journal Article
• Authors: Kim, Hyun S.; Shaib, Walid L.; Zhang, Chao; Nagaraju, Ganji Purnachandra; Wu, Christina; Alese, Olatunji B.; Chen, Zhengjia; Brutcher, Edith; Renfroe, Meredith; El‐Rayes, Bassel F.
• Is Part Of: Cancer. Volume 124:Issue 9(2018)
• Page Start: 1992
• Page End: 2000
• Publication Date: 2018-02-16
• Subjects: everolimus -- liver metastasis -- pasireotide -- phase 1b -- selective internal radioembolization (SIRT) -- unresectable neuroendocrine tumor; Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.31192
• Languages: English
• ISSNs: 0008-543X

Abstract

Abstract : BACKGROUND: Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT. METHODS: This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2.5, 5, and 10 mg/day), pasireotide (600 μg twice daily), and SIRT (SIR‐Spheres dose on days 9 and 37). Eligibility criteria included well or moderately differentiated NETs, bilobar liver metastases, and progression on long‐acting octreotide. Toxicities and responses were evaluated with the Common Terminology Criteria for Adverse Events and the Response Evaluation Criteria in Solid Tumors (version 1.1). Dose‐limiting toxicities (DLTs) were defined in the first 28 days. Correlative markers—angiopoietin 1, angiopoietin 2, basic fibroblast growth factor, collagen V, insulin‐like growth factor binding protein 1, insulin‐like growth factor binding protein 1, interleukin 8, M30, M65, placenta growth factor, and vascular endothelial growth factor receptor 2—were assessed. The Norfolk Quality of Life–Neuroendocrine Tumor Questionnaire was used to assess the quality of life (QOL). RESULTS: Thirteen patients were enrolled; 1 was not evaluable for the primary endpoint. Eleven patients had well‐differentiated tumors. The primary sites included small bowel (4), pancreas (3), lung (2), colon (1), gastric (1), and unknown primary (2) were unknown. Four had liver‐only disease; 12 completed the planned treatment. No DLTs were observed. There was no treatment‐related mortality. The most common toxicity was hyperglycemia. Clinically significant liver toxicity was not observed. One patient had liver progression. QOL improved on treatment. The median progression‐free survival and overall survival were 18.6 and 46.3 months, respectively. CONCLUSIONS: The recommended phase 2 dose of everolimus is 10 mg daily in combination with pasireotide and SIRT. The regimen is well tolerated. Preliminary activity appears promising. Cancer 2018;124:1992‐2000. © 2018 American Cancer Society . Abstract : In combination with pasireotide and selective internal radioembolization, everolimus at 10 mg daily is well tolerated with no significant liver toxicities. The activity of this combination is promising in terms of response and survival.