Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis

被引：68

作者：

Fazio, Nicola ^{[1
]}

Buzzoni, Roberto ^{[2
]}

Delle Fave, Gianfranco ^{[3
]}

Tesselaar, Margot E. ^{[4
]}

Wolin, Edward ^{[5
]}

Van Cutsem, Eric ^{[6
,7
]}

Tomassetti, Paola ^{[8
]}

Strosberg, Jonathan ^{[9
]}

Voi, Maurizio ^{[10
]}

Bubuteishvili-Pacaud, Lida ^{[11
]}

Ridolfi, Antonia ^{[12
]}

Herbst, Fabian ^{[11
]}

Tomasek, Jiri ^{[13
]}

Singh, Simron ^{[14
]}

Pavel, Marianne ^{[15
]}

Kulke, Matthew H. ^{[16
]}

Valle, Juan W. ^{[17
]}

Yao, James C. ^{[18
]}

机构：

[1] IRCCS, European Inst Oncol, Milan, Italy

[2] Fdn IRCCS Fdn, Natl Inst Tumors, Milan, Italy

[3] Univ Roma La Sapienza, Hosp St Andrea, Rome, Italy

[4] Antoni van Leeuwenhoek, Netherlands Canc Inst, Amsterdam, Netherlands

[5] Montefiore Einstein Ctr Canc Care, Bronx, NY USA

[6] Univ Hosp Gasthuisberg, Leuven, Belgium

[7] Katholieke Univ Leuven, Leuven, Belgium

[8] Univ Bologna, S Orsola Malpighi Hosp, Dept Med & Surg Sci, Bologna, Italy

[9] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA

[10] Novartis Pharmaceut, E Hanover, NJ USA

[11] Novartis Pharma AG, Basel, Switzerland

[12] Novartis Pharma SAS, Rueil Malmaison, France

[13] Masaryk Univ, Masaryk Mem Canc Inst, Fac Med, Brno, Czech Republic

[14] Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada

[15] Charite Univ Med Berlin, Campus Virchow Klinikum, Berlin, Germany

[16] Dana Farber Canc Inst, Boston, MA 02115 USA

[17] Univ Manchester, Christie NHS Fdn Trust, Inst Canc Sci, Manchester, Lancs, England

[18] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

来源：

CANCER SCIENCE | 2018年 / 109卷 / 01期

关键词：

everolimus; lung carcinoid; neuroendocrine tumors; progression-free survival; RADIANT-4; PHASE-II; OCTREOTIDE; MANAGEMENT; GUIDELINES; NEOPLASMS; DIAGNOSIS; SURVIVAL; DISEASE; UPDATE; TRIAL;

D O I：

10.1111/cas.13427

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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).

引用

页码：174 / 181

页数：8

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