Value of a molecular screening program to support clinical trial enrollment in Asian cancer patients: The Integrated Molecular Analysis of Cancer (IMAC) Study.
Valerie HeongNicholas Li-Xun SynXiao Wen LeeNur Sabrina SapariXue Qing KohZul Fazreen Adam IsaJoey Sy LimDiana LimBrendan PangYee Liang ThianLai Kuan NgAndrea L WongRoss Andrew SooWei Peng YongCheng Ean CheeSoo-Chin LeeBoon-Cher GohRichie SoongDavid S P TanPublished in: International journal of cancer (2017)
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, 1.5-4.0 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.
Keyphrases
- clinical trial
- end stage renal disease
- chronic kidney disease
- copy number
- ejection fraction
- newly diagnosed
- peritoneal dialysis
- squamous cell carcinoma
- palliative care
- mitochondrial dna
- epithelial mesenchymal transition
- patient reported outcomes
- dna methylation
- quality improvement
- free survival
- health insurance
- hiv infected
- papillary thyroid
- smoking cessation
- transcription factor
- phase ii
- patient reported
- tyrosine kinase
- phase iii