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.
Resources from the same session
3905 - Loss of CDX-2 expression is an independent poor prognostic biomarker in colorectal cancer
Presenter: Krittiya Korphaisarn
Session: Poster Display session 2
Resources:
Abstract
3963 - Robot-assisted natural orifice specimen extraction surgery for radical resection of colorectal cancer
Presenter: Zhengchuan Niu
Session: Poster Display session 2
Resources:
Abstract
3989 - Bevacizumab as adjuvant treatment for colon cancer: Updated results from the AVANT phase III Study by the GERCOR Group
Presenter: Thierry André
Session: Poster Display session 2
Resources:
Abstract
4741 - Real world data on adjuvant chemotherapy for high-risk stage II colorectal cancer – the role of tumor side
Presenter: Camila Araujo de Carvalho
Session: Poster Display session 2
Resources:
Abstract
4973 - Oncological Outcome and Safety of Bevacizumab (BV) Therapy in Patients with Occlusive Colon Cancer and Self-Expandable Metal Stents (SEMS)
Presenter: Vilma Pacheco-Barcia
Session: Poster Display session 2
Resources:
Abstract
2295 - Active chronic hepatitis B increases the risk of liver metastasis of colorectal cancer- a retrospective clinical study of 7187 consecutive cases of newly diagnosed colorectal cancer
Presenter: Lei Zhao
Session: Poster Display session 2
Resources:
Abstract
3845 - Comprehensive Evaluation of Recurrence Risk (CERR) Score for Colorectal Liver Metastases: Development and Validation
Presenter: Wei Ye
Session: Poster Display session 2
Resources:
Abstract
1976 - BRAF-mutated colorectal metastases: what is the benefit of liver surgery? Results from a cohort of 91 patients.
Presenter: Sahir Javed
Session: Poster Display session 2
Resources:
Abstract
2688 - The smallest colorectal liver metastasis size as a prognosis factor after laparoscopic liver resection
Presenter: Baptiste Cervantes
Session: Poster Display session 2
Resources:
Abstract
4961 - Validation of GAME score risk groups in resected colorectal cancer liver metastases and the prognostic relevance of KRAS, NRAS and BRAF mutation analysis
Presenter: Berta Martin-Cullell
Session: Poster Display session 2
Resources:
Abstract