Meeting
2015 Gastrointestinal Cancers Symposium
EGFR ligands and ERCC1 mRNA expression to predict clinical outcome in Japanese (JPN) patients (pts) with metastatic colorectal cancer (mCRC) harboring overexpressed EGFR and KRAS exon 2 wild-type (KRAS wt) treated with cetuximab (cet) plus oxaliplatin-based chemotherapy (JACCRO CC-05/06 AR).
Authors
Yu Sunakawa
University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA
Yu Sunakawa , Wataru Ichikawa , Akihito Tsuji , Miriana Moran , Stephanie H. Astrow , Dongyun Yang , Wu Zhang , Takehiro Takahashi , Tadamichi Denda , Ken Shimada , Mitsugu Kochi , Masato Nakamura , Masahito Kotaka , Yoshihiko Segawa , Masahiro Takeuchi , Heinz-Josef Lenz , Masashi Fujii , Toshifusa Nakajima
Organizations
University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, Showa University, Tokyo, Japan, Department of Medical Oncology, Kobe City Medical Center General Hospital, Hyogo, Japan, Response Genetics Inc., Los Angeles, CA, USC Norris Comprehensive Cancer Center, Los Angeles, CA, Showa University Hospital, Tokyo, Japan, Chiba Cancer Center, Chiba, Japan, Showa University Koutou Toyosu Hospital, Tokyo, Japan, Nihon University School of Medicine, Tokyo, Japan, Aizawa Hospital, Matsumoto, Japan, Sano Hospital, Kobe, Japan, Department of Medical Oncology, Saitama Medical University International Medical Center, Hidaka, Japan, Kitasato University School of Pharmacy, Tokyo, Japan, Japan Clinical Cancer Research Organization, Tokyo, Japan
Research Funding
No funding sources reported
Background: Previous studies have reported that EGFR ligands, amphiregulin (AREG) and epiregulin (EREG), are potential predictive markers for cet and high ERCC1 expression is associated with resistance to platinum-containing chemotherapy. However, there are still few studies to assess predictive values of these expression levels in JPN mCRC pts. The aim of this study was to evaluate the values in JPN mCRC pts treated with cet. Methods: This study enrolled 77 pts with tissue available from 2 prospective clinical trials evaluating combination of cet with oxaliplatin-based chemotherapy as first-line treatment in pts with KRAS wt and EGFR-expressing tumors, modified FOLFOX6 (n=28/57, UMIN000004197) and SOX (n=49/67, UMIN000007022). Total RNA isolated by macro-dissection from tissue was screened by RT-PCR for mRNA expression levels of AREG, EREG, and ERCC1, the cut-off values of which were based on the optimal cut-off value using the maximal chi-square approach on tumor response with adjusted p values. The same cut-off values were used to evaluate associations with progression-free survival (PFS) and overall survival (OS). Results: Median age and follow-up time were 63 (range: 39-79) years old and 24.7 (range: 5.5-39.3) months, respectively. In 73 evaluable pts, response rate (RR) was 77 % (95% CI, 67 to 86), but no significant association was seen in RR. Pts with high AREG expression (>1.59) had significantly longer PFS (11.6 vs. 6.6 months, HR: 0.53, logrank p=0.047) but not OS in 67 assessable pts. Pts with low ERCC1 expression (≤1.35) had significantly longer OS (42.8 vs. 22.0 months, HR: 2.46, logrank p=0.014) but a trend toward longer PFS (11.6 vs. 8.9 months, HR: 1.63, logrank p=0.092) in 68 assessable pts. On the other hand, high EREG expression (>3.21) was not associated with clinical outcome in 64 assessable pts. Conclusions: Our study identified predictive roles for AREG and ERCC1 mRNA expression in JPN mCRC pts treated with cet plus oxaliplatin. However, extended RAS mutations analysis is warranted (UMIN000010635).
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Abstract Details
Session Type
Poster Session
Session Title
General Poster Session C: Cancers of the Colon, Rectum, and Anus
Track
Cancers of the Colon, Rectum, and Anus
Sub Track
Translational Research
Citation
J Clin Oncol 33, 2015 (suppl 3; abstr 618)
DOI
10.1200/jco.2015.33.3_suppl.618
Abstract #
618
Poster Bd #
C10
Abstract Disclosures
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