@article{2e6ea030874f4324bc70354fbf9cfa30,
title = "Everolimus in Neuroendocrine Tumors of the Gastrointestinal Tract and Unknown Primary",
abstract = "Purpose: The RADIANT-4 randomized phase 3 study demonstrated significant prolongation of median progression-free survival (PFS) with everolimus compared to placebo (11.0 [95% CI 9.2-13.3] vs. 3.9 [95% CI 3.6-7.4] months) in patients with advanced, progressive, nonfunctional gastrointestinal (GI) and lung neuroendocrine tumors (NET). This analysis specifically evaluated NET patients with GI and unknown primary origin. Methods: Patients in the RADIANT-4 trial were randomized 2:1 to everolimus 10 mg/day or placebo. The effect of everolimus on PFS was evaluated in patients with NET of the GI tract or unknown primary site. Results: Of the 302 patients enrolled, 175 had GI NET (everolimus, 118; placebo, 57) and 36 had unknown primary (everolimus, 23; placebo, 13). In the GI subset, the median PFS by central review was 13.1 months (95% CI 9.2-17.3) in the everolimus arm versus 5.4 months (95% CI 3.6-9.3) in the placebo arm; the hazard ratio (HR) was 0.56 (95% CI 0.37-0.84). In the unknown primary patients, the median PFS was 13.6 months (95% CI 4.1-not evaluable) for everolimus versus 7.5 months (95% CI 1.9-18.5) for placebo; the HR was 0.60 (95% CI 0.24-1.51). Everolimus efficacy was also demonstrated in both midgut and non-midgut populations; a 40-46% reduction in the risk of progression or death was reported for patients in the combined GI and unknown primary subgroup. Everolimus had a benefit regardless of prior somatostatin analog therapy. Conclusions: Everolimus showed a clinically meaningful PFS benefit in patients with advanced progressive nonfunctional NET of GI and unknown primary, consistent with the overall RADIANT-4 results, providing an effective new standard treatment option in this patient population and filling an unmet treatment need for these patients.",
keywords = "Everolimus, Gastrointestinal tract, Neuroendocrine tumors, RADIANT-4 study",
author = "{RAD001 in Advanced Neuroendocrine Tumors, Fourth Trial (RADIANT-4) Study Group} and Simron Singh and Carlo Carnaghi and Roberto Buzzoni and Pommier, {Rodney F.} and Markus Raderer and Jiri Tomasek and Harald Lahner and Valle, {Juan W.} and Maurizio Voi and Lida Bubuteishvili-Pacaud and Jeremie Lincy and Edward Wolin and Natsuko Okita and Libutti, {Steven K.} and Oh, {Do Youn} and Matthew Kulke and Jonathan Strosberg and Yao, {James C.} and Pavel, {Marianne E.} and Nicola Fazio",
note = "Funding Information: S.S. has received honoraria, consulting or advisory fees, travel and accommodation expenses, and research funding from Novar-tis. R.B. has received research funding from Italfarmaco, Novartis, and Otsuka and travel and accommodation expenses from Ipsen, Italfarmaco, and Novartis. R.F.P. has received consulting fees and is on the speakers{\textquoteright} bureau for Novartis. M.R. has received honoraria from Celgene, Ipsen, Novartis, and Roche and consulting or advisory fees from Celgene, Ipsen, Novartis, and Roche. J.T. has received honoraria, research funding, and travel and accommodation expenses from Novartis. H.L. has received honoraria from Ipsen, Novartis, and Pfizer, consulting or advisory fees from No-vartis and Pfizer, research funding from Novartis, and travel and accommodation expenses from Ipsen, Novartis, and Pfizer. J.W.V. has received honoraria, consulting or advisory fees and research funding from Novartis. M.V. and L.B.-P. are employees of and own shares in Novartis. C.C., J.L., and D.-Y.O. declare no conflicts of interest. E.W. has received consulting or advisory fees from Cel-gene, Ipsen, and Novartis. N.O. has received research funding from Novartis, Teijin, Otsuka, and Taiho. S.K.L. has received travel and accommodation expenses and research funding from Oxi-gene. M.K. has received consulting or advisory fees from Ipsen and Novartis. J.S. has received honoraria from Novartis, consulting or advisory fees from Ipsen, Lexicon, and Novartis, research funding from Novartis and Pfizer, and is on the speakers{\textquoteright} bureau for Bayer and Genentech. J.C.Y. has received consulting or advisory fees from Ipsen, Lexicon, and Novartis and research funding from No-vartis. M.E.P. has received honoraria from Ipsen, Lexicon, Novar-tis, and Pfizer, consulting or advisory fees from Ipsen, Lexicon, Novartis, and Pfizer, research funding from Novartis, and travel and accommodation expenses from Ipsen and Novartis. N.F. has received honoraria from Ipsen and Novartis, consulting or advisory fees from Ipsen, Lexicon, Novartis, and Italfarmaco, research funding from Novartis, and travel and accommodation expenses from Ipsen and Novartis. Funding Information: The authors acknowledge the patients, their families, and their caregivers, as well as the investigators and research nurses. The RADIANT-4 study group is grateful to all the physicians who contributed to the present study and to the worldwide network of re-search nurses, trial coordinators, and operations staff for their contributions. We appreciate the support of the colleagues of the RA-DIANT-4 study team who contributed to the presented data. In addition, we thank Anamika Gulati from Novartis Healthcare Pvt. Ltd. for providing medical editorial assistance. We would like to thank Caroline Sachs for her contributions to the study. This study was funded by Novartis Pharmaceuticals Corporation. Funding Information: This study was funded by Novartis Pharmaceuticals Corporation. Publisher Copyright: {\textcopyright} 2017 S. Karger AG, Basel.",
year = "2018",
month = apr,
day = "1",
doi = "10.1159/000477585",
language = "English (US)",
volume = "106",
pages = "211--220",
journal = "Neuroendocrinology",
issn = "0028-3835",
publisher = "S. Karger AG",
number = "3",
}