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Yutaka Fujiwara
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Lunch & Poster Display session (ID 58)
- Event: ELCC 2019
- Type: Poster Display session
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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181TiP - Phase II study of crizotinib in Japanese patients with advanced non-small cell lung cancer harboring a MET gene alteration: Co-MET study (ID 170)
12:30 - 13:00 | Author(s): Yutaka Fujiwara
- Abstract
Background
The majority of non-small cell lung cancer (NSCLC) patients are diagnosed as metastatic disease for which no curative treatment is available. Phase III randomized trials of tyrosine kinase inhibitor (TKI) therapy for EGFR-mutant and anaplastic lymphoma receptor tyrosine kinase (ALK)-rearranged lung cancers have documented improvements in response and progression-free survival (PFS), and TKIs are approved for the treatment of patients with oncogene-driver mutations. c-Met is the tyrosine kinase receptor for hepatocyte growth factor, and MET gene alterations including MET exon14 skipping mutation-positive or MET high gene copy number are known to be an oncogene via activation of c-MET signaling pathway. Crizotinib is a selective ATP-competitive small-molecule inhibitor of c-Met, ALK and ROS1 tyrosine kinases. Durable responses to crizotinib were reported in patients with advanced NSCLC harboring MET exon 14 skipping mutation or high MET gene copy number. Therefore, we considered to assess the efficacy and safety of crizotinib in patients with advanced NSCLC harboring a MET gene alteration.
a9ded1e5ce5d75814730bb4caaf49419 Trial design
Co-MET is an open-label, multi-center, 2 cohort single-arm phase II trial of oral crizotinib in patients with advanced NSCLC harboring MET exon 14 skipping mutations without prior MET TKI treatment (cohort 1) or high MET gene copy number of 7 or more (cohort 2). The status of MET gene alterations will be determined using a validated RT-PCR assay and/or NGS. Crizotinib, 250 mg BID, will be administered orally continuously until disease progression or unacceptable toxicities. All tumor scans will be reviewed by an independent radiology committee according to RECIST version 1.1. The primary endpoint is objective response rate (ORR). Assuming a null hypothesis of a 20% ORR and an alternative hypothesis of a 50% ORR for cohort 1, and a one-sided type I error of 0.05 (one-side) and 80% power based on the exact binomial distribution, the required number of evaluable patients is 19. The sample size for cohort 2 is empirically set at 10 patients. Clinical trial information: UMIN000031623.
d9b324a48b043b3d87bc9b3fe620f260 Clinical trial identification
UMIN000031623.
7a6a3ffa2dadc03a6151ee2c4d6fa383 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
Japan Agency for Medical Research and Development.
682889d0a1d3b50267a69346a750433d Disclosure
K. Nosaki, S. Matsumoto: Honoraria: Pfizer Japan Inc. T. Seto: Honoraria, research grants: Pfizer Japan Inc. H. Murakami: Personal fees: Pfizer Japan Inc. K. Goto: Honoraria, research funding: Pfizer Japan Inc. K. Yoh: Research funding: Pfizer Japan Inc. All other authors have declared no conflicts of interest.
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4P - Correlation between folate receptor alpha (FRα) expression and clinicopathological features in lung adenocarcinoma (ID 245)
12:30 - 13:00 | Author(s): Yutaka Fujiwara
- Abstract
Background
FRα is present on the cell surface, mediates its intracellular transport via receptor-mediated endocytosis, and is also involved in cell division. FRα is expressed at high levels on various cancer cells, and it is considered that FRα could be a potential therapeutic target in FRα-expressing cancers.
a9ded1e5ce5d75814730bb4caaf49419 Methods
We investigated the correlations between FRα expression in tissue microarray (TMA) constructed from surgical specimens of lung adenocarcinoma (LADC) and clinicopathological features including EGFR mutation retrospectively. Two TMA cores per a resected LADC specimen were created using TMA Master (3DHISTECH, Budapest, Hungary) at National Cancer Center Hospital between January 2007 and November 2016. Based on previous studies, if the percentage of stained tumor cells was greater than or equal 5%, FRα was considered as positive, and if H-score was more than or equal 60 (range, 0-300), FRα was considered as high expression.
20c51b5f4e9aeb5334c90ff072e6f928 Results
Overall, 466 TMA cores created from 233 patients who underwent surgery for LADC were evaluated; FRα positive expression (FRα-pos)/negative (FRα-neg), 222/11; FRα high expression (FRα-HE)/low (FRα-LE), 190/43, respectively. 124 patients (53.2%) were with EGFR mutation. The median H-scores of FRα expression, rates of FRα-pos, and rates of FRα-HE for EGFR mutation and wild type were 159/104 (p = 0.0002), 97.6/92.7% (p = 0.077), and 88.7/73.4% (p = 0.0026). The median disease free survival (months) were 18.7/23.3 (p = 0.30) for FRα-pos/neg and 20.2/12.8 (p = 0.42) for FRα-HE/LE, respectively. The median overall survival were 92.9/not reached (p = 0.42) for FRα-pos/neg and 92.9/96.4 (p = 0.42) for FRα-HE/LE, respectively. FRα expression was not considered as a prognostic factor in LADC. 82 patients with EGFR mutation received EGFR-TKI after recurrence (FRα-pos/neg, 79/3; FRα-HE/LE, 71/11). Overall response rates and median progression free survival (months) of EGFR-TKI were 59.2/66.6% (p = 0.80) and 16.1/11.5 (p = 0.016) for FRα-pos/neg; 61.8/45.5% (p = 0.31) and 16.2/13.2 (p = 0.95) for FRα-HE/LE, respectively.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
FRα expression was significantly higher in LADC with EGFR mutation than that with wild-type. The efficacy of EGFR-TKI was better in FRα-pos than in FRα-neg.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
Has not received any funding.
682889d0a1d3b50267a69346a750433d Disclosure
Y. Fujiwara: Research funding: AbbVie, AstraZeneca, BMS, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Incyte, Merck Serono, MSD, Novartis; Advisory role: AstraZeneca, BMS, MSD, Novartis, ONO; Speakers bureau: AstraZeneca, BMS, MSD, Novartis, ONO, Sysmex, Taiho. S. Kitano: Personal fee, grant: Eisai; Honoraria: ONO, Bristol-Myers Squibb, AstraZeneca, Chugai, Pfizer, Sanofi, Nippon Kayaku, Boehringer Ingelheim, Meiji, Taiho, Novartis, Daiichi Sankyo, MSD, Kirin, Celgene, Sumitomo Dainippon; Grant: Regeneron, Astellas, Gilead, AMED, JSPS. T. Shimizu: Advisory board: Takeda, The Consortium on Harmonization of Institutional Requirements for Clinical Research; Corporate sponsored research: Bristol-Myers Squibb, Daiichi Sankyo, Lilly, Novartis, Eisai, Takeda, PharmaMar, FivePrime, 3D-Medicine, Symbio, Chordia. N. Yamamoto: Grants: Quintiles, Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Kirin, Takeda, ONO, Janssen, Lilly, MSD, Merck; Advisory: Eisai, Takeda, Otsuka, Boehringer Ingelheim, Cimic; Speakers: BMS, Pfizer, AstraZeneca, Lilly, ONO, Chugai. N. Motoi: Personal fee (lecture, Advisory board): Bristol-Myers Squibb, Miraca Life Sciences, AstraZeneca, Chugai Pharma, MSD, Agilent, Novartis, Roche Diagnostics; Institutional research funding: Roche Diagnostics. All other authors have declared no conflicts of interest.
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