Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 2

1259 - Prognostic and Predictive Impact On FMS-like Tyrosine Kinase 3 (FLT3) Amplification In Patients With Metastatic Colorectal Cancer

Date

29 Sep 2019

Session

Poster Display session 2

Topics

Tumour Site

Colon and Rectal Cancer

Presenters

Hiroko Hasegawa

Citation

Annals of Oncology (2019) 30 (suppl_5): v198-v252. 10.1093/annonc/mdz246

Authors

H. Hasegawa1, H. Taniguchi2, T. Kato3, S. Fujii4, H. Ebi5, M. Shiozawa6, S. Yuki7, T. Masuishi8, K. Kato9, N. Izawa10, T. Moriwaki11, Y. Kagawa12, Y. Sakamoto13, W. Okamoto13, Y. Nakamura2, K. Yamazaki14, T. Yoshino2

Author affiliations

  • 1 Gastroenterology And Hepatology, National Hospital Organization Osaka National Hospital, 540-0006 - Osaka/JP
  • 2 Gastroenterology And Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 3 Surgery, Osaka National Hospital, 5400006 - Osaka/JP
  • 4 Division Of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 277-8577 - Kashiwa/JP
  • 5 Molecular Therapeutics, Aichi Cancer Center Research Institute, 4648681 - Nagoya/JP
  • 6 Gastrointestinal Surgery, Kanagawa Cancer Center, 2410815 - Yokohama/JP
  • 7 Gastroenterology And Hepatology, Hokkaido University Hospital, 0608648 - Sapporo/JP
  • 8 Clinical Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 9 Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo/JP
  • 10 Clinical Oncology, St. Marianna University School of Medicine, 2168511 - Kawasaki/JP
  • 11 Gastroenterology, Faculty of Medicine, University of Tsukuba,, 3050005 - Tsukuba/JP
  • 12 Surgery, Kansai Rosai Hospital, 6600064 - Amagasaki/JP
  • 13 Clinical Research Support Office, Biobank Translational Research Support Section, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 14 Gastroenterology, Sizuoka Cancer Center, 4118777 - Shizuoka/JP

Resources

Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 1259

Background

FMS-like tyrosine kinase 3 (FLT3) plays a key role in hematopoiesis, and FLT3-associated molecular alterations are an established predictor for the treatment with FLT3 inhibitors in acute myeloid leukemia. However, the oncogenic role of FLT3 amplification (amp) in patients (pts) with metastatic colorectal cancer (mCRC) has not yet been well established.

Methods

Tumor tissue samples from 2,329 mCRC pts were sequenced using next-generation sequencing (NGS) with Oncomine Comprehensive Assay in the Nationwide Cancer Genome Screening Project in Japan (SCRUM-Japan GI-SCREEN). Clinicopathological features, co-altered genes, prognosis and regorafenib efficacy on FLT3 amp (defined as copy number ≥ 7.0) vs. non-FLT3 amp mCRC were investigated.

Results

Between Apr 2015 and Jun 2018, a total of 85 pts (3.6%) with mCRC with FLT3 amp were observed. There were no clear differences in baseline characteristics between pts with or without FLT3 amp. The enrichment of TP53 mutation in FLT3 amp mCRC was observed more frequently than non-FLT3 amp (74.1% vs. 64.7%, P = 0.08), but RAS mutation frequency was similar in both (48.2% vs. 42.8%, P = 0.31). In contrast, activating alterations in BRAF (1.1% vs. 7.1%, P = 0.053) and PIK3CA (1.1% vs 7.0%, P = 0.03) mutations were both less frequent in FLT3 amp vs. non-FLT3 amp mCRC. Median OS from 1st-line chemotherapy in FLT3 amp mCRC was significantly shorter than those in non-FLT3 amp (30.2 vs. 43.4 months, P = 0.002). Furthermore, in 20 pts receiving regorafenib, a multikinase inhibitor with a mild inhibitory activity of FLT3, the disease control rate (DCR) was higher in FLT3 amp mCRC pts (n = 7) compared with non-FLT3 amp (57.1% vs. 23.0 %, P = 0.13).

Conclusions

FLT3 amp was associated with a significantly worse survival and a higher DCR from regorafenib, suggesting it has a distinct oncogenic role in mCRC. Further investigation of the oncogenic role of FLT3 amp in mCRC is warranted in clinical trials.

Clinical trial identification

UMIN000016344.

Editorial acknowledgement

Legal entity responsible for the study

SCRUM-Japan.

Funding

17 SCRUM-Japan Collaborating Pharmaceutical Companies, AMED, NCC.

Disclosure

H. Taniguchi: Research grant / Funding (self): Takeda; Advisory / Consultancy: Chugai; Advisory / Consultancy: Taiho. T. Kato: Honoraria (self): Chugai Pharmaceutical; Advisory / Consultancy: Takeda; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Bayer; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Yakult Honsya. S. Yuki: Speaker Bureau / Expert testimony: Chugai Pharma; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Bayer Yakuhin; Speaker Bureau / Expert testimony: Ono Pharmaceutical; Speaker Bureau / Expert testimony: Pharma International; Speaker Bureau / Expert testimony: Daiichi Sankyo; Speaker Bureau / Expert testimony: Takeda Pharmaceutical; Speaker Bureau / Expert testimony: Eli Lilly Japan; Speaker Bureau / Expert testimony: Taiho Pharmaceutical; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: Yakult Honsha; Speaker Bureau / Expert testimony: Merck Biopharma. T. Masuishi: Honoraria (self): Eli Lilly; Honoraria (self): Chugai Pharma; Honoraria (self): Merck Serono; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Yakult Honsya. K. Kato: Research grant / Funding (self): Shionogi; Research grant / Funding (self): Ono Pharmaceutical; Research grant / Funding (self): Merck Serono. N. Izawa: Advisory / Consultancy: Taiho Pharmaceutical; Advisory / Consultancy: Sanofi; Advisory / Consultancy: MSD; Advisory / Consultancy: Bayer; Advisory / Consultancy: Bristol-Myers; Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck Serono. T. Moriwaki: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): MSD; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Yakult Honsha; Research grant / Funding (institution): Eisai; Speaker Bureau / Expert testimony: Chugai Pharma; Speaker Bureau / Expert testimony: Yakult Honsha; Speaker Bureau / Expert testimony: Merck Serono; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: Liliy Japan; Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Ono Pharmaceutical. Y. Kagawa: Speaker Bureau / Expert testimony: Chugai; Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy: Sanofi; Speaker Bureau / Expert testimony: Taiho. W. Okamoto: Research grant / Funding (institution): MSD. Y. Nakamura: Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Taiho Pharmaceutical. K. Yamazaki: Honoraria (self): Daiichi Sankyo; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Eli Lilly; Honoraria (self): Merck Serono; Honoraria (self), Research grant / Funding (institution): Taiho Pharma; Honoraria (self): Bayer Yakuhin. T. Yoshino: Research grant / Funding (institution): Chugai pharma; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Sumitomo Dainippon pharma; Research grant / Funding (institution): Glaxo SmithKline. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.