TY - JOUR
T1 - Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors
T2 - RADIANT-4 lung subgroup analysis
AU - Fazio, Nicola
AU - Buzzoni, Roberto
AU - Delle Fave, Gianfranco
AU - Tesselaar, Margot E.
AU - Wolin, Edward
AU - Van Cutsem, Eric
AU - Tomassetti, Paola
AU - Strosberg, Jonathan
AU - Voi, Maurizio
AU - Bubuteishvili-Pacaud, Lida
AU - Ridolfi, Antonia
AU - Herbst, Fabian
AU - Tomasek, Jiri
AU - Singh, Simron
AU - Pavel, Marianne
AU - Kulke, Matthew H.
AU - Valle, Juan W.
AU - Yao, James C.
N1 - Funding Information:
Nicola Fazio received honoraria from Novartis, Ipsen, and Pfizer, and his institution received research funding from Novartis and Merck Serono. Gianfranco Delle Fave received honoraria and research funding from Novartis. Margot Tesselaar received research funding from Novartis. Eric Van Cutsem received research funding from Novartis, Ipsen, Sanofi, Roche, Bayer, and Boehringer. Jonathan Strosberg received research funding from Novartis and Ipsen and his institution received research funding from Novartis. Maurizio Voi and Fabian Herbst are employees of Novartis and have stock ownership from Novartis. Lida Bubuteishvili-Pacaud and Antonia Ridolfi are employees of Novartis. Simron Singh received research funding from Novartis. Marianne Pavel received honoraria from Novartis and her institution received research funding from Novartis. Juan W. Valle received honoraria and travel reimbursement from Novartis, and his institution received research funding from Novartis. James C. Yao received honoraria and research funding from Novartis. The study was designed under the responsibility of Novartis Pharmaceutical Corporation, in conjunction with the steering committee. The study was funded by Novartis Pharmaceutical Corporation. Everolimus was provided by Novartis Pharmaceutical Corporation. Novartis Pharmaceutical Corporation collected and analyzed the data and contributed to the interpretation of the study. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication. Roberto Buzzoni, Edward Wolin, Paola Tomassetti, Jiri Tomasek, and Matthew H. Kulke have no conflict of interest.
Funding Information:
Funding information Novartis Pharmaceuticals Corporation. The authors acknowledge the patients, their families, and their caregivers, as well as all the investigators. The RADIANT-4 study group is grateful to all the physicians who contributed to the present study, and the worldwide network of research nurses, trial coordinators, and operations staff for their contributions. We appreciate the support of the colleagues of the RADIANT-4 Study Team who contributed to the presented data. In addition, we thank Rajasree Solipuram, PhD, Novartis Healthcare Pvt. Ltd. for providing medical editorial assistance with this manuscript.
Publisher Copyright:
© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
PY - 2018/1
Y1 - 2018/1
N2 - In the phase III RADIANT-4 study, everolimus improved median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated (grade 1 or grade 2), non-functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.67; P <.00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT-4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8-10.9) months in the everolimus arm vs 3.6 (1.9-5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28-0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3-4 drug-related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well-differentiated, non-functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT-4 cohort. These results support the use of everolimus in patients with advanced, non-functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783).
AB - In the phase III RADIANT-4 study, everolimus improved median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated (grade 1 or grade 2), non-functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.67; P <.00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT-4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8-10.9) months in the everolimus arm vs 3.6 (1.9-5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28-0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3-4 drug-related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well-differentiated, non-functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT-4 cohort. These results support the use of everolimus in patients with advanced, non-functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783).
KW - RADIANT-4
KW - everolimus
KW - lung carcinoid
KW - neuroendocrine tumors
KW - progression-free survival
UR - http://www.scopus.com/inward/record.url?scp=85040667811&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040667811&partnerID=8YFLogxK
U2 - 10.1111/cas.13427
DO - 10.1111/cas.13427
M3 - Article
C2 - 29055056
AN - SCOPUS:85040667811
SN - 1347-9032
VL - 109
SP - 174
EP - 181
JO - Cancer Science
JF - Cancer Science
IS - 1
ER -
