Open AccessEverolimus in advanced, progressive, well‐differentiated, non‐functional neuroendocrine tumors: RADIANT ‐4 lung subgroup analysis
Author(s) -
Fazio Nicola,
Buzzoni Roberto,
Delle Fave Gianfranco,
Tesselaar Margot E.,
Wolin Edward,
Van Cutsem Eric,
Tomassetti Paola,
Strosberg Jonathan,
Voi Maurizio,
BubuteishviliPacaud Lida,
Ridolfi Antonia,
Herbst Fabian,
Tomasek Jiri,
Singh Simron,
Pavel Marianne,
Kulke Matthew H.,
Valle Juan W.,
Yao James C.
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13427
Subject(s) - everolimus , medicine , placebo , clinical endpoint , hazard ratio , gastroenterology , adverse effect , oncology , confidence interval , surgery , randomized controlled trial , pathology , alternative medicine
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 ( NET s) 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 NET s. 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. NCT 01524783).