Phase II trial of cabozantinib in patients with carcinoid and pancreatic neuroendocrine tumors (pNET).

• DOI: 10.1200/jco.2017.35.4_suppl.228
• Publication Date: 2017-03-21T17:08:11Z
• Authors: Jennifer A. Chan; Jason Edward Faris; Janet E. Murphy; Lawrence Scott Bl...; Eunice Lee Kwak; Nadine Jackson Mc...; Charles S. Fuchs; Jeffrey A. Meyerh...; Kimmie Ng; Andrew X. Zhu; Thomas Adam Abrams; Brian M. Wolpin; Sui Zhang; Amanda Reardon; Bridget Fitzpatrick; Matthew H. Kulke; David P. Ryan
• Keywords: Cabozantinib; Discontinuation; Clinical endpoint; Carcinoid tumors

228 Background: Activation of VEGFR2 and c-MET has been implicated in driving growth neuroendocrine tumors (NET); additionally, expression associated with shorter survival. Cabozantinib inhibits c-MET. We performed a two-cohort phase II study to evaluate the efficacy cabozantinib patients (pts) advanced carcinoid or pNET (NCT01466036). Methods: Pts progressive, well differentiated, grade 1-2 were enrolled parallel cohorts treated 60 mg po qd . There was no limit prior therapy. restaged every 2 mos for first 6 mos, then 3 mos. The primary endpoint objective response rate as measured by RECIST 1.1. Enrollment approximately 35 each tumor type planned. Results: 41 pts (median age 63 yrs, 44% male, % ECOG PS 0/1 = 51/49) accrued. Accrual cohort halted due investigator/sponsor decision after 20 55 60% 40/60). Carcinoid completed median 8 (range 0-44) 28-day treatment cycles; 10 (0-35) cycles. 14 remain on treatment. Reasons discontinuation progression death (51%), withdrawal consent investigator (28%), adverse events (AE, 21%). 3/20 achieved PR (ORR 15%, 95% CI 5-36%); 15/20 had SD. 6/41 7-28%); 26/41 SD Median PFS 21.8 mo (95% CI, 8.5-32.0 mo) 31.4 8.5 mo-NR) carcinoid. Gr 3/4 toxicity ≥ 1 pt included hypertension (13%), hypophosphatemia (11%), diarrhea (10%), lymphopenia (7%), thrombocytopenia (5%), fatigue increased lipase amylase (8%). Unexpected AEs heart failure autoimmune hemolytic anemia, pt. 81% 53 completing more than cycle required dose reduction from initial dose. Conclusions: Treatment responses encouraging durations pNET. While common, tolerable. Further evaluation is warranted both NET subgroups. Clinical trial information: NCT01466036.