Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
`Vol 22, No 14S (July 15 Supplement), 2004: 4124
`© 2004 American Society of Clinical Oncology
`
`Abstract
`
`A phase II trial of imatinib in patients with advanced
`carcinoid tumor
`K. Carr, J. C. Yao, A. Rashid, S.-C. Yeung, J. Szklaruk, J. Baker, J.-N. Vauthey, S. Curley,
`L. Ellis and J. A. Ajani
`
`University of Texas M. D. Anderson Cancer Center, Houston, TX
`
`4124
`
`Background: Effective systemic therapy options for carcinoid tumors are lacking. Carcinoid
`tumors co-express PDGF and PDGFR, a receptor/ligand system important in cell growth and
`survival. A phase II trial was conducted to assess the response rate and safety profile of PDGFR
`inhibitor, imatinib (Gleevec TM), at a dose of 400 mg PO BID in patients with advanced carcinoid
`tumors. Methods: Previously treated or untreated patients with advanced carcinoid tumors with
`adequate organ and bone marrow function were included. Response was evaluated every 12
`weeks by CT or MRI. Results: 15 men and 12 women with a median age of 60 (22–74) enrolled.
`21 patients received concurrent octreotide. 10, 6, 3 and 2 patients received prior chemotherapy,
`hepatic artery embolization, interferon, and radiation, respectively. Median number of weeks on
`study was 16 (range, 12–78+). By RECIST criteria, 1 patient, receiving concurrent octreotide,
`had a radiologic PR (remains on study after 1.5 years), 17 had SD, and 9 with PD. Among 14
`patients with PD at entry, 8 patients remained progression free for at least 12 weeks (range, 18–
`52+). 4 patients had > 50% reduction in markers (chromogranin, 5-HIAA, pancreatic
`polypeptide). Median PFS duration is 24 weeks (range, 12–68+). PFS duration was significantly
`better in patients receiving concurrent octreotide (14 weeks vs 38 weeks; P=0.05). 1-year OS rate
`is 88%. There was no correlation between plasma VEGF and bFGF, CT flow studies and patient
`outcome. Grade 3–4 toxicities included fatigue (7), hypophosphatemia (5), diarrhea (3), fluid
`retention (3), nausea (2), granulocytopenia (2), hypokalemia (2), rash (1), anorexia (1),
`thrombocytopenia (1), hyperglycemia (1), and hyperbilirubinemia (1). Conclusions: Our data
`suggest a modest level of biologic effect of imatinib in carcinoid, therefore, further development
`of imatinib in conjunction with other agents may be warranted. Supported by a grant from
`Novartis.
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`NOVARTIS EXHIBIT 2049
`Par v. Novartis, IPR 2016-01479
`Page 1 of 1
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