Japanese Foundation for Cancer Research, Tokyo, Japan
Yuta Ushida , Eiji Shinozaki , Keisho Chin , Mitsukuni Suenaga , Daisuke Takahari , Masato Ozaka , Mariko Ogura , Takashi Ichimura , Takeru Wakatsuki , TOMOHIRO MATSUSHIMA , Hiroki Osumi , Yumiko Ota , Kensei Yamaguchi
Background: Several studies have reported that patients with right-sided colon cancers (RCC) have more unfavorable responses to anti-epidermal growth factor receptor (EGFR) antibody therapy than those with left-sided colon cancers (LCC). One of the causes is that RCC have more frequently genetic mutations such as RAS, BRAF, and PIK3CA than LCC. We investigated clinical outcomes of RCC patients treated with anti-EGFR antibody in the later line without these mutations. Methods: We reviewed 653 cases of colorectal cancer treated with anti-EGFR antibody from October 2009 to July 2017. There were 150 cases of RCC patients. Among them, 32 patients without KRAS status and 54 patients without enough genetic samples for gene re-analysis were excluded. We extracted 64 patients with status on RAS, BRAF, and PIK3CA , and finally enrolled 25 patients treated with anti-EGFR antibody plus irinotecan or anti-EGFR antibody alone in the later line. We analyzed the relationship of molecular status with clinical outcomes; overall response rate (RR), overall survival (OS) and progression-free survival (PFS) in this retrospective study. Results: Overall, there were 48% of cases with any mutations; among them 8.0% for KRAS, 4.0% for NRAS, 24.0% for BRAF and 4.0% for PIK3CA. Twenty percent of patients were treated as 2nd line therapy, while 72%, 16% treated as 3rd, 4th line therapy. RR of all cases, those whom without KRAS, RAS, RAS or BRAF, any mutations were 16.0%, 19.1%, 20.0%, 28.6%, 30.8%. The median OS and PFS in all wild-type patients were tended to be better than in those of all cases (OS; 14.9 vs. 11.6 months, hazard ratio = 0.70, p = 0.30, PFS; 8.17 vs. 5.37 months, hazard ratio = 0.67, p = 0.24). Conclusions: Even if primary tumors are in right-sided colon, in the enriched and selected patients anti-EGFR antibody therapy showed enough antitumor activity. Anti-EGFR antibody for RCC cases without using it at the front line is an effective option in the later line.
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