Value of a molecular screening program to support clinical trial enrollment in Asian cancer patients: The Integrated Molecular Analysis of Cancer (IMAC) Study
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 oc...
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| Published in: | International journal of cancer Vol. 142; no. 9; pp. 1890 - 1900 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Wiley Subscription Services, Inc
01-05-2018
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | 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.
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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. |
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| Bibliography: | DSPT consults on the advisory board for Astra Zeneca, Merck Sharp & Dohme (MSD), Hoffmann‐La Roche, Novartis and Bayer, and has received research funding from Karyopharm Therapeutics and Astra Zeneca. RS has received sponsorship from AstraZeneca, Merck, Biorad, Illumina, Perkin Elmer and ThermoFisher, and research funding from AstraZeneca, Bayer, Illumina, Kyowa Hakka Kirin and Roche. Following the submission of the present manuscript to the International Journal of Cancer Conflict of interest Role of the Funder/Support RS has also become a full‐time employee of Innovations Exchange Pte Ltd. The results of the IMAC study were presented in part as an oral abstract at the European Society of Medical Oncology Asia Congress on Dec 18, 2017 (Abstract no. 149O). This manuscript reports additional outcomes and updated results after a longer follow‐up period. The NMRC had no involvement in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication. V.H and N.L.S. contributed equally to this work ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0020-7136 1097-0215 |
| DOI: | 10.1002/ijc.31091 |