Real-time tumor gene expression profiling to direct gastric cancer chemotherapy

Proof-of-concept "3G" trial

Wei Peng Yong, SunYoung 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, Hyuncheol Chung, Matthew C.H. Ng, David Wai Meng Tai, Ming Hui Lee, Jeanie Wu, Khay Guan Yeoh & 1 others Patrick Tan

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)5272-5281
Number of pages10
JournalClinical Cancer Research
Volume24
Issue number21
DOIs
Publication statusPublished - 2018 Nov 1

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Gene Expression Profiling
oxaliplatin
Stomach Neoplasms
Drug Therapy
Neoplasms
Cisplatin
Transcriptome
Research Design
Biomarkers
Therapeutics
Research

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Yong, Wei Peng ; Rha, SunYoung ; Tan, Iain Bee Huat ; Choo, Su Pin ; Syn, Nicholas L. ; Koh, Vivien ; Tan, Shi Hui ; Asuncion, Bernadette Reyna ; Sundar, Raghav ; So, Jimmy Bok Yan ; Shabbir, Asim ; Tan, Chee Seng ; Kim, Hyo Song ; Jung, Minkyu ; Chung, Hyuncheol ; Ng, Matthew C.H. ; Tai, David Wai Meng ; Lee, Ming Hui ; Wu, Jeanie ; Yeoh, Khay Guan ; Tan, Patrick. / Real-time tumor gene expression profiling to direct gastric cancer chemotherapy : Proof-of-concept "3G" trial. In: Clinical Cancer Research. 2018 ; Vol. 24, No. 21. pp. 5272-5281.
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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.",
author = "Yong, {Wei Peng} and SunYoung Rha and Tan, {Iain Bee Huat} and Choo, {Su Pin} and Syn, {Nicholas L.} and Vivien Koh and Tan, {Shi Hui} and Asuncion, {Bernadette Reyna} and Raghav Sundar and So, {Jimmy Bok Yan} and Asim Shabbir and Tan, {Chee Seng} and Kim, {Hyo Song} and Minkyu Jung and Hyuncheol Chung and Ng, {Matthew C.H.} and Tai, {David Wai Meng} and Lee, {Ming Hui} and Jeanie Wu and Yeoh, {Khay Guan} and Patrick Tan",
year = "2018",
month = "11",
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doi = "10.1158/1078-0432.CCR-18-0193",
language = "English",
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pages = "5272--5281",
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Yong, WP, Rha, S, Tan, IBH, Choo, SP, Syn, NL, Koh, V, Tan, SH, Asuncion, BR, Sundar, R, So, JBY, Shabbir, A, Tan, CS, Kim, HS, Jung, M, Chung, H, Ng, MCH, Tai, DWM, Lee, MH, Wu, J, Yeoh, KG & Tan, P 2018, 'Real-time tumor gene expression profiling to direct gastric cancer chemotherapy: Proof-of-concept "3G" trial', Clinical Cancer Research, vol. 24, no. 21, pp. 5272-5281. https://doi.org/10.1158/1078-0432.CCR-18-0193

Real-time tumor gene expression profiling to direct gastric cancer chemotherapy : Proof-of-concept "3G" trial. / Yong, Wei Peng; Rha, SunYoung; Tan, Iain Bee Huat; Choo, Su Pin; Syn, Nicholas L.; Koh, Vivien; Tan, Shi Hui; Asuncion, Bernadette Reyna; Sundar, Raghav; So, Jimmy Bok Yan; Shabbir, Asim; Tan, Chee Seng; Kim, Hyo Song; Jung, Minkyu; Chung, Hyuncheol; Ng, Matthew C.H.; Tai, David Wai Meng; Lee, Ming Hui; Wu, Jeanie; Yeoh, Khay Guan; Tan, Patrick.

In: Clinical Cancer Research, Vol. 24, No. 21, 01.11.2018, p. 5272-5281.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Real-time tumor gene expression profiling to direct gastric cancer chemotherapy

T2 - Proof-of-concept "3G" trial

AU - Yong, Wei Peng

AU - Rha, SunYoung

AU - Tan, Iain Bee Huat

AU - Choo, Su Pin

AU - Syn, Nicholas L.

AU - Koh, Vivien

AU - Tan, Shi Hui

AU - Asuncion, Bernadette Reyna

AU - Sundar, Raghav

AU - So, Jimmy Bok Yan

AU - Shabbir, Asim

AU - Tan, Chee Seng

AU - Kim, Hyo Song

AU - Jung, Minkyu

AU - Chung, Hyuncheol

AU - Ng, Matthew C.H.

AU - Tai, David Wai Meng

AU - Lee, Ming Hui

AU - Wu, Jeanie

AU - Yeoh, Khay Guan

AU - Tan, Patrick

PY - 2018/11/1

Y1 - 2018/11/1

N2 - 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.

AB - 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.

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