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Observational Study
. 2021 Jan;112(1):314-322.
doi: 10.1111/cas.14693. Epub 2020 Nov 20.

FMS-like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer

Hiroko Hasegawa  1 , Hiroya Taniguchi  2   3 , Yoshiaki Nakamura  2   3 , Takeshi Kato  4 , Satoshi Fujii  5   6 , Hiromichi Ebi  7 , Manabu Shiozawa  8 , Satoshi Yuki  9 , Toshiki Masuishi  10 , Ken Kato  11 , Naoki Izawa  12 , Toshikazu Moriwaki  13 , Eiji Oki  14 , Yoshinori Kagawa  15 , Tadamichi Denda  16 , Tomohiro Nishina  17 , Akihito Tsuji  18 , Hiroki Hara  19 , Taito Esaki  20 , Tomohiro Nishida  21 , Hisato Kawakami  22 , Yasutoshi Sakamoto  3 , Izumi Miki  3 , Wataru Okamoto  3   23 , Kentaro Yamazaki  24 , Takayuki Yoshino  2
Affiliations
Observational Study

FMS-like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer

Hiroko Hasegawa et al. Cancer Sci. 2021 Jan.

Abstract

FMS-like tyrosine kinase 3 (FLT3) plays a key role in hematopoiesis. However, the oncogenic role of FLT3 amplification in patients with metastatic colorectal cancer (mCRC) remains unclear. Here, we aimed to evaluate the characteristics, prognosis, and treatment efficacy of an FLT3 inhibitor (regorafenib) in patients with mCRC with FLT3 amplifications. Tumor tissue samples from 2329 patients were sequenced using NGS in the Nationwide Cancer Genome Screening Project in Japan. The effects of clinicopathological features, co-altered genes, prognosis, and efficacy of regorafenib were investigated. Between April 2015 and June 2018, 85 patients with mCRC with FLT3 amplification were observed. There were no differences in baseline characteristics between patients with or without FLT3 amplification. The frequency of RAS or other gene co-alterations was inversely correlated with the copy number status. Median survival time in patients with FLT3 amplification was significantly shorter compared with those with non-FLT3 amplification. Further investigations of FLT3 amplification as a potential treatment target in mCRC are warranted.

Keywords: FLT3 amplification; colorectal cancer; copy number status; next-generation sequencing; prognosis.

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Conflict of interest statement

Hiroya Taniguchi received research funding from Eli Lilly Japan Co., Ltd., Takeda, and Daiichi Sankyo. Yoshiaki Nakamura received research funding from Taiho Pharmaceutical. Satoshi Yuki received research funding from Chugai Pharmaceutical Co., Ltd. and Eli Lilly Japan Co., Ltd. Toshikazu Moriwaki received research honoraria from Taiho Pharmaceutical Co., Ltd and Chugai Pharmaceutical Co., Ltd. Eiji Oki received honoraria from Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Eli Lilly Japan Co., Ltd. Akihito Tuji received honoraria from Taiho Pharmaceutical Co., Ltd. and Chugai Pharmaceutical Co., Ltd. Takayuki Yoshino received research funding from Novartis Pharma KK, Chugai Pharmaceutical Co., Ltd., and Daiichi Sankyo. All other authors have nothing to declare.

Figures

FIGURE 1
FIGURE 1
Flow diagram of this study. amp, amplification
FIGURE 2
FIGURE 2
Long tail plots for FLT3 amplified metastatic colorectal cancer. A, Concurrent genomic alterations in FLT3 low‐amplified cases (n = 40). B, Concurrent genomic alterations in FLT3 high‐amplified cases (n = 45)
FIGURE 3
FIGURE 3
Overlapping alterations on chromosome 13 and other potential driver genes in FLT3 amplified metastatic colorectal cancer. A, Overlapping alterations in FLT3 low‐amplified cases (n = 40). B, Overlapping alterations in FLT3 high‐amplified cases (n = 45). amp, amplification; mt, mutation
FIGURE 4
FIGURE 4
Overall survival according to FLT3 amplification status. Kaplan‐Meier curve for patients with high FLT3 amplification (n = 26, blue) and low FLT3 amplification (n = 20, green), and those without FLT3 amplification (n = 1019, red). amp, amplification; CI, confidence interval; HR, hazard ratio; OS, overall survival
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