In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e15566-e15566
Kurzfassung:
e15566 Background: As a central component of PI3K/AKT pathway, AKT serves as an attractive target of anti-cancer strategy with various AKT inhibitors, which show great promise in phase I/II clinical trials. This study aimed to investigate AKT1/2/3 status in different types of cancers by using next generation sequencing (NGS). Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor samples were collected from 10,010 Chinese patients with solid tumors and subjected to next-generation sequencing (NGS)-based 450 gene panel testing carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Genomic alterations, tumor mutational burden (TMB) values, and microsatellite instability (MSI) status were assessed with a mean coverage of 1000X, including single base substitutions, short and long insertion/deletions, copy number variations, gene fusions, and rearrangements. Genomic data and immune checkpoint inhibitors (ICIs) treatment outcome of a cohort of 1610 patients with solid tumors were derived from cBioPortal (MSKCC, Nat Genet. 2019). Results: AKT1/2/3 were found to be mutually exclusive with each other and accounted for 3.4% in this cohort. The frequencies of AKT1/2/3 variations were 1.1%, 1.6%, and 0.8%, respectively. The most common co-altered genes associated with AKT1/2/3 variations were TP53 (69.4%), PIK3CA (19.3%), KRAS (19%), CCNE1 (18.4%), CDKN2A (16.6%), and 11q13 (6.5%). AKT1/2/3 variations were significantly associated with higher TMB, and independent of MSI status. Outcome data from the MSKCC cohort showed that patients with AKT1/2/3 variations had a remarkable clinical benefit to ICIs treatment compared to patients with wild-type AKT1/2/3 in overall survival (OS) (NA vs 18 months, p = 0.009). Furthermore, AKT1/2/3 variations were independent risk factors of OS (HR: 0.55, 95%CI: 0.34-0.87, p = 0.012). Conclusions: The prevalence of AKT1/2/3 somatic alterations across different types of solid tumors in China was 3.4%. AKT1/2/3 variations were associated with an increased TMB and favorable response to ICIs, suggesting that A KT1/2/3 variations may be biomarkers for guiding anti-AKT agents and ICI treatment.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.e15566
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2020
ZDB Id:
2005181-5
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