Dual MEK/AKT inhibition with trametinib and GSK2141795 does not yield clinical benefit in metastatic NRAS-mutant and wild-type melanoma

被引：44

作者：

Algazi, Alain P. ^{[1
]}

Esteve-Puig, Rosaura ^{[2
]}

Nosrati, Adi ^{[2
]}

Hinds, Brian ^{[3
]}

Hobbs-Muthukumar, Adele ^{[1
]}

Nandoskar, Prachi ^{[1
]}

Ortiz-Urda, Susana ^{[2
]}

Chapman, Paul B. ^{[4
]}

Daud, Adil ^{[1
]}

机构：

[1] UCSF Melanoma Oncol, San Francisco, CA 94143 USA

[2] UCSF Dermatol, San Francisco, CA USA

[3] UCSD Dermatopathol, La Jolla, CA USA

[4] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

来源：

PIGMENT CELL & MELANOMA RESEARCH | 2018年 / 31卷 / 01期

关键词：

AKT; GSK2141795; MEK; melanoma; NRAS; trametinib; wild type; UVEAL MELANOMA; SURVIVAL; BRAF; ASSOCIATION; COMBINATION; TUMORS;

D O I：

10.1111/pcmr.12644

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Aberrant MAPK and PI3K pathway signaling may drive the malignant phenotype in NRAS-mutant and BRAF(WT) NRAS(WT) metastatic melanoma. To target these pathways, NRAS-mutant and BRAF(WT) NRAS(WT) patients received oral trametinib at 1.5mg daily and GSK2141795 at 50mg daily in a two-cohort Simon two-stage design. Participants had adequate end-organ function and no more than two prior treatment regimens. Imaging assessments were performed at 8-week intervals. A total of 10 NRAS-mutant and 10 BRAF(WT) NRAS(WT) patients were enrolled. No objective responses were noted in either cohort. The median PFS and OS were 2.3 and 4.0 months in the NRAS-mutant cohort and 2.8 and 3.5 months in the wild-type cohort. Grade 3 and grade 4 adverse events, primarily rash, were observed in 25% of patients. We conclude that the combination of trametinib and GSK2141795 does not have significant clinical activity in NRAS-mutant or BRAF(WT) NRAS(WT) melanoma.

引用

页码：110 / 114

页数：5