lunes, 16 de octubre de 2017

Value of a molecular screening program to support clinical trial enrollment in Asian cancer patients: The Integrated Molecular Analysis of Cancer (... - PubMed - NCBI

Value of a molecular screening program to support clinical trial enrollment in Asian cancer patients: The Integrated Molecular Analysis of Cancer (... - PubMed - NCBI





 2017 Oct 9. doi: 10.1002/ijc.31091. [Epub ahead of print]

Value of a molecular screening program to support clinical trial enrollment in Asian cancer patients: The Integrated Molecular Analysis of Cancer (IMAC) Study.

Heong V1,2Syn NL1,2Lee XW1Sapari NS2Koh XQ2Adam Isa ZF2Lim JS2Lim D3,4Pang B2,3,4Thian YL5Ng LK3Wong AL1,2Soo RA1,2Yong WP1,2Chee CE1Lee SC1,2Goh BC1,2,6Soong R2,3Tan DSP1,2,7.

Abstract

The value of precision oncology initiatives in Asian contexts remains unresolved. Here we review the institutional implementation of prospective molecular screening to facilitate accrual of patients into biomarker-driven clinical trials, and to explore the mutational landscape of advanced tumors occurring in a prospective cohort of Asian patients (n = 396) with diverse cancer types. Next-generation sequencing (NGS) and routine clinicopathological assays such as immunohistochemistry, copy number analysis, and in situ hybridization tests were performed on tumor samples. Actionable biomarker results were used to identify eligibility for early-phase, biomarker-driven clinical trials. Overall, NGS was successful in 365 of 396 patients (92%), achieving a mean depth of 1,943× and coverage uniformity of 96%. The median turnaround time from sample receipt to return of genomic results was 26.0 days (IQR, 19.0-39.0 days). Reportable mutations were found in 300 of 365 patients (82%). Ninety-one percent of patients at study enrollment indicated consent to receive incidental findings and willingness to undergo genetic counseling if required. The most commonly mutated oncogenes included KRAS (19%), PIK3CA (16%), EGFR (5%), BRAF (3%), and KIT (3%); while the most frequently mutated tumor suppressor genes included TP53 (40%), SMARCB1 (12%), APC (8%), PTEN (6%), and SMAD4 (5%). Among 23 patients enrolled in genotype-matched trials, median progression-free survival was 2.9 months (IQR, 1.5 to 4.0 months). Nine of 20 evaluable patients (45%; 95% CI, 23.1% to 68.5%) derived clinical benefit, including 3 partial responses and 6 with stable disease lasting ≥ 8 weeks. This article is protected by copyright. All rights reserved.

KEYWORDS:

Biomarker-driven clinical trials; Next-generation sequencing; Precision Medicine; Precision oncology; Targeted therapy

PMID:
 
28994108
 
DOI:
 
10.1002/ijc.31091

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