期刊
INTERNATIONAL JOURNAL OF CANCER
卷 142, 期 9, 页码 1890-1900出版社
WILEY
DOI: 10.1002/ijc.31091
关键词
precision oncology; precision medicine; next-generation sequencing; targeted therapy; biomarker-driven clinical trials
类别
资金
- Singapore Ministry of Health's National Medical Research Council (NMRC)
- National Research Foundation Singapore
- Singapore Ministry of Education
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 1,943x 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, 1.5-4.0 months). Nine of 20 evaluable patients (45%; 95% CI, 23.1-68.5%) derived clinical benefit, including 3 partial responses and 6 with stable disease lasting >= 8 weeks. What's new? Variability in genomic mutations across ethnicities and geographical regions potentially complicates clinical trials using predictive and prognostic biomarkers. In this study, the authors review the institutional implementation of a prospective molecular screening protocol in an Asian population. The spectrum and prevalence of somatic mutations was determined. Molecular prescreening was found to be critical to the enrollment of 8 percent of patients into biomarker-enriched clinical trials. About 91 percent of patients indicated interest in being informed of incidental findings. Patients enrolled in trials showed signs of benefit, with a progression-free survival of 2.9 months and clinical benefit rate of 45 percent.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据