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Real-Time Tumor Gene Expression Profiling to Direct Gastric Cancer Chemotherapy: Proof-of-Concept "3G" Trial

Authors
 Wei Peng Yong  ;  Sun Young Rha  ;  Iain Bee-Huat Tan  ;  Su-Pin Choo  ;  Nicholas L. Syn  ;  Vivien Koh  ;  Shi-Hui Tan  ;  Bernadette Reyna Asuncion  ;  Raghav Sundar  ;  Jimmy Bok-Yan So  ;  Asim Shabbir  ;  Chee-Seng Tan  ;  Hyo-Song Kim  ;  Minkyu Jung  ;  Hyun Cheol Chung  ;  Matthew C.H. Ng  ;  David Wai-Meng Tai  ;  Ming-Hui Lee  ;  Jeanie Wu  ;  Khay Guan Yeoh  ;  Patrick Tan 
Citation
 Clinical Cancer Research, Vol.24(21) : 5272-5281, 2018 
Journal Title
 Clinical Cancer Research 
ISSN
 1078-0432 
Issue Date
2018
Abstract
Purpose: The oxaliplatin plus S-1 and cisplatin plus S-1 regimens are interchangeably used in the management of advanced gastric cancer. The previously reported G-intestinal (G1) and G-diffuse (G2) intrinsic gene expression signatures showed promise for stratifying patients according to their tumor sensitivity to oxaliplatin or cisplatin.Experimental Design: The proof-of-concept, multicenter, open-label phase II "3G" trial was done to prospectively evaluate the feasibility and efficacy of using genomic classifiers to tailor treatment in gastric cancer. Patients' tumors were classified as "G1" or "G2" using a nearest-prediction template method, or "G3" (unclear assignment) when FDR ≥ 0.05. The first 30 patients in the "G1" cohort were assigned oxaliplatin plus S-1 (SOX) chemotherapy; thereafter, subsequently recruited "G1" patients were treated with cisplatin plus S-1 (SP) chemotherapy. "G2" patients and "G3" patients were treated with SP and SOX chemotherapy, respectively.Results: A total of 48, 21, and 12 patients, respectively, were given "G1," "G2," and "G3" genomic assignments. Median turnaround time was 7 days (IQR, 5-9). Response rates were 44.8%, 8.3%, 26.7%, and 55.6% for the "G1-SOX," "G1-SP," "G2," "G3" cohorts, respectively; and was higher in G1 patients treated with SOX compared with SP (P = 0.033). Exploratory analyses using the genomic classifier of Lei and colleagues validated the utility of the metabolic signature as a biomarker for predicting benefit from chemotherapy (log-rank P = 0.004 for PFS), whereas the Asian Cancer Research Group classifier did not demonstrate any predictive value.Conclusions: This bench-to-bedside effort establishes a reasonable turnaround time for gene expression profiling and possible utility of genomic classifiers in gastric cancer treatment stratification.
Full Text
http://clincancerres.aacrjournals.org/content/24/21/5272.long
DOI
10.1158/1078-0432.CCR-18-0193
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
김효송(Kim, Hyo Song) ORCID logo https://orcid.org/0000-0002-0625-9828
라선영(Rha, Sun Young) ORCID logo https://orcid.org/0000-0002-2512-4531
정민규(Jung, Min Kyu) ORCID logo https://orcid.org/0000-0001-8281-3387
정현철(Chung, Hyun Cheol) ORCID logo https://orcid.org/0000-0002-0920-9471
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/166693
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