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Value of a molecular screening program to support clinical trial enrollment in Asian cancer patients: The Integrated Molecular Analysis of Cancer (IMAC) Study
Author(s) -
Heong Valerie,
Syn Nicholas L.,
Lee Xiao Wen,
Sapari Nur Sabrina,
Koh Xue Qing,
Adam Isa Zul Fazreen,
Sy Lim Joey,
Lim Diana,
Pang Brendan,
Thian Yee Liang,
Ng Lai Kuan,
Wong Andrea L.,
Soo Ross Andrew,
Yong Wei Peng,
Chee Cheng Ean,
Lee SooChin,
Goh BoonCher,
Soong Richie,
Tan David S.P.
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31091
Subject(s) - kras , medicine , biomarker , oncology , pten , cancer , clinical trial , prospective cohort study , institutional review board , colorectal cancer , surgery , biology , genetics , apoptosis , pi3k/akt/mtor pathway
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.