3 years ago

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

Yee Liang Thian, Xue Qing Koh, Nicholas L. Syn, Cheng Ean Chee, Xiao Wen Lee, Zul Fazreen Adam Isa, Boon-Cher Goh, Lai Kuan Ng, Brendan Pang, Richie Soong, Soo-Chin Lee, Diana Lim, Joey SY Lim, David S.P. Tan, Nur Sabrina Sapari, Andrea L. Wong, Wei Peng Yong, Valerie Heong, Ross Andrew Soo
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.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/ijc.31091

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