TY - JOUR
T1 - aCGH Analysis of Predictive Biomarkers for Response to Bevacizumab plus Oxaliplatin- or Irinotecan-Based Chemotherapy in Patients with Metastatic Colorectal Cancer
AU - Fujita, Yoshihiko
AU - Taguri, Masataka
AU - Yamazaki, Kentaro
AU - Tsurutani, Junji
AU - Sakai, Kazuko
AU - Tsushima, Takahiro
AU - Nagase, Michitaka
AU - Tamagawa, Hiroshi
AU - Ueda, Shinya
AU - Tamura, Takao
AU - Tsuji, Yasushi
AU - Murata, Kohei
AU - Taira, Koichi
AU - Denda, Tadamichi
AU - Moriwaki, Toshikazu
AU - Funai, Sadao
AU - Nakajima, Takako Eguchi
AU - Muro, Kei
AU - Tsuji, Akihito
AU - Yoshida, Motoki
AU - Suyama, Koichi
AU - Kurimoto, Takuya
AU - Sugimoto, Naotoshi
AU - Baba, Eishi
AU - Seki, Nobuhiko
AU - Sato, Mikio
AU - Shimura, Takaya
AU - Boku, Narikazu
AU - Hyodo, Ichinosuke
AU - Yamanaka, Takeharu
AU - Nishio, Kazuto
N1 - Funding Information:
We thank Okumoto K. and Kitayama T. for technical support and Marco A. De Velasco for critically reading the manuscript. We also thank the patients who participated in WJOG4407GTR and their families, WJOG4407G investigators, nurses, and other medical staffs who contributed to the study, and the Data and Safety Monitoring Committee (H. Ariyoshi), Audit Committee (Y. Nakanishi) of the West Japanese Oncology Group (WJOG), and the WJOG Data Center (K. Mori, N. Ozumi, and S. Nakamura). This work was sponsored by the WJOG, a nonprofit organization. The WJOG received unrestricted research grants from Pharmaceutical companies disclosed at http://www.wjog.jp/support.html.
Publisher Copyright:
© AlphaMed Press 2018
PY - 2019/3
Y1 - 2019/3
N2 - Background: The randomized phase III study (WJOG4407G) showed equivalent efficacy between FOLFOX and FOLFIRI in combination with bevacizumab as the first-line treatment for metastatic colorectal cancer (mCRC). We studied whole genome copy number profiles using array-based comparative genomic hybridization (aCGH) analysis of tumor tissue samples obtained in this study. The aim of this study was to identify gene copy number alterations that could aid in selecting either FOLFOX or FOLFIRI in combination with bevacizumab for patients with mCRC. Materials and Methods: DNA was purified from 154 pretreatment formalin-fixed paraffin-embedded tissue samples (75 from the FOLFOX arm and 79 from the FOLFIRI arm) of 395 patients enrolled in the WJOG4407G trial and analyzed by aCGH. Genomic regions greater than 1.2-fold were regarded as copy number gain (CNG). Results: Patient characteristics between the treatment arms were well balanced except for tumor laterality (left side; 64% in FOLFOX arm and 80% in FOLFIRI arm, p =.07). FOLFIRI showed a trend toward better response rate (RR), progression-free survival (PFS) and overall survival (OS) than FOLFOX in the patients with CNG of chromosome 8q24.1 (Fisher's exact test, p =.134 for RR; interaction test, p =.102 for PFS and p =.003 for OS) and 8q24.2 (Fisher's exact test, p =.179 for RR; interaction test, p =.144 for PFS and p =.002 for OS). Conclusion: Chromosome 8q24.1–q24.2 may contain genes that could potentially serve as predictive markers for selecting either FOLFOX or FOLFIRI in combination with bevacizumab for treatment of patients with mCRC. Implications for Practice: Bevacizumab has been used as a standard first-line treatment for patients with metastatic colorectal cancer (mCRC) in combination with either oxaliplatin-based or irinotecan-based chemotherapy. Until now, there has been no predictive marker to choose between the two combination chemotherapies. This array-based comparative genomic hybridization analysis revealed that the difference in therapeutic effect between the two combination chemotherapies is prominent in patients with mCRC with gene copy number gain in chromosome 8p24.1–p24.2. Such patients showed more favorable response and survival when treated with irinotecan-based combination chemotherapy. Overlapping genes commonly found in this region may be predictive biomarkers of the efficacy of the combination chemotherapy with bevacizumab.
AB - Background: The randomized phase III study (WJOG4407G) showed equivalent efficacy between FOLFOX and FOLFIRI in combination with bevacizumab as the first-line treatment for metastatic colorectal cancer (mCRC). We studied whole genome copy number profiles using array-based comparative genomic hybridization (aCGH) analysis of tumor tissue samples obtained in this study. The aim of this study was to identify gene copy number alterations that could aid in selecting either FOLFOX or FOLFIRI in combination with bevacizumab for patients with mCRC. Materials and Methods: DNA was purified from 154 pretreatment formalin-fixed paraffin-embedded tissue samples (75 from the FOLFOX arm and 79 from the FOLFIRI arm) of 395 patients enrolled in the WJOG4407G trial and analyzed by aCGH. Genomic regions greater than 1.2-fold were regarded as copy number gain (CNG). Results: Patient characteristics between the treatment arms were well balanced except for tumor laterality (left side; 64% in FOLFOX arm and 80% in FOLFIRI arm, p =.07). FOLFIRI showed a trend toward better response rate (RR), progression-free survival (PFS) and overall survival (OS) than FOLFOX in the patients with CNG of chromosome 8q24.1 (Fisher's exact test, p =.134 for RR; interaction test, p =.102 for PFS and p =.003 for OS) and 8q24.2 (Fisher's exact test, p =.179 for RR; interaction test, p =.144 for PFS and p =.002 for OS). Conclusion: Chromosome 8q24.1–q24.2 may contain genes that could potentially serve as predictive markers for selecting either FOLFOX or FOLFIRI in combination with bevacizumab for treatment of patients with mCRC. Implications for Practice: Bevacizumab has been used as a standard first-line treatment for patients with metastatic colorectal cancer (mCRC) in combination with either oxaliplatin-based or irinotecan-based chemotherapy. Until now, there has been no predictive marker to choose between the two combination chemotherapies. This array-based comparative genomic hybridization analysis revealed that the difference in therapeutic effect between the two combination chemotherapies is prominent in patients with mCRC with gene copy number gain in chromosome 8p24.1–p24.2. Such patients showed more favorable response and survival when treated with irinotecan-based combination chemotherapy. Overlapping genes commonly found in this region may be predictive biomarkers of the efficacy of the combination chemotherapy with bevacizumab.
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U2 - 10.1634/theoncologist.2018-0119
DO - 10.1634/theoncologist.2018-0119
M3 - Article
C2 - 30425180
AN - SCOPUS:85056622565
VL - 24
SP - 327
EP - 337
JO - Oncologist
JF - Oncologist
SN - 1083-7159
IS - 3
ER -
