Details of a Researcher - Hirata, Kenro

A Phase II Study of FOLFIRI Plus Ziv-Aflibercept After Trifluridine/Tipiracil Plus Bevacizumab in Patients with Metastatic Colorectal Cancer: WJOG 11018G

Matsumoto T., Yamamoto Y., Kotaka M., Masuishi T., Tsuji Y., Shoji H., Hirata K., Tsuduki T., Makiyama A., Izawa N., Takahashi N., Tsuda M., Yasui H., Ohta T., Kito Y., Otsu S., Hironaka S., Yamazaki K., Boku N., Hyodo I., Yoshimura K., Muro K.

Targeted Oncology （Targeted Oncology) 19 （ 2 ） 181 - 190 2024.03

ISSN 17762596

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Background: Non-inferiority of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) to irinotecan/fluoropyrimidine plus BEV in metastatic colorectal cancer was investigated in the phase III TRUSTY study, and we conducted a phase II study of FOLFIRI (5-FU+leucovorin+irinotecan) plus zib-aflibercept (AFL) after FTD/TPI plus BEV. However, the TRUSTY study failed during the recruitment of our patients. Objective: We present the findings of a phase II study on the efficacy of FOLFIRI plus zib-aflibercept (AFL) after FTD/TPI plus BEV, including clinical results with plasma biomarker analyses. Methods: This was a multicenter, single-arm, phase II study in patients with metastatic colorectal cancer refractory or intolerant to oxaliplatin, fluoropyrimidine, BEV, and FTD/TPI. The primary endpoint was progression-free survival. Fifteen plasma angiogenesis-associated biomarkers were analyzed using a Luminex® multiplex assay U-kit. Results: Between January 2020 and May 2022, 26 patients (median age, 68 years) from 15 sites were enrolled. The median progression-free survival was 4.9 months (85% confidence interval, 3.4 month–not estimated). The overall response and disease control rates were 8% and 62%, respectively. The median levels of vascular endothelial growth factor-A and placental growth factor, both targets of AFL, were below the measurable limit of 30 pg/mL and 16 pg/mL, respectively. Patients were divided into two groups at the median levels of baseline biomarkers. The progression-free survival did not differ between high and low expressers of placental growth factor (p = 0.7), while it tended to be shorter in those with high levels of osteopontin (p = 0.05), angiopoietin-2 (p = 0.07), and tissue inhibitor of matrix metalloproteinases-1 (p = 0.1). Conclusions: This study did not meet the primary endpoint. Hence, FOLFIRI plus AFL should not be used after FTD/TPI plus BEV for metastatic colorectal cancer. Further studies are needed to determine factors not targeted by AFL that may affect the efficacy of the treatment. Clinical Trial Registration: jRCTs041190100.
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Pre-existing Interstitial Lung Abnormalities and Immune Checkpoint Inhibitor-Related Pneumonitis in Solid Tumors: A Retrospective Analysis

Horiuchi K., Ikemura S., Sato T., Shimozaki K., Okamori S., Yamada Y., Yokoyama Y., Hashimoto M., Jinzaki M., Hirai I., Funakoshi T., Mizuno R., Oya M., Hirata K., Hamamoto Y., Terai H., Yasuda H., Kawada I., Soejima K., Fukunaga K.

Oncologist （Oncologist) 29 （ 1 ） E108 - E117 2024.01

ISSN 10837159

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Background: Immune checkpoint inhibitors (ICIs) have demonstrated efficacy over previous cytotoxic chemotherapies in clinical trials among various tumors. Despite their favorable outcomes, they are associated with a unique set of toxicities termed as immune-related adverse events (irAEs). Among the toxicities, ICI-related pneumonitis has poor outcomes with little understanding of its risk factors. This retrospective study aimed to investigate whether pre-existing interstitial lung abnormality (ILA) is a potential risk factor for ICI-related pneumonitis. Materials and Methods: Patients with non-small cell lung cancer, malignant melanoma, renal cell carcinoma, and gastric cancer, who was administered either nivolumab, pembrolizumab, or atezolizumab between September 2014 and January 2019 were retrospectively reviewed. Information on baseline characteristics, computed tomography findings before administration of ICIs, clinical outcomes, and irAEs were collected from their medical records. Pre-existing ILA was categorized based on previous studies. Results: Two-hundred-nine patients with a median age of 68 years were included and 23 (11.0%) developed ICI-related pneumonitis. While smoking history and ICI agents were associated with ICI-related pneumonitis (P = .005 and .044, respectively), the categories of ILA were not associated with ICI-related pneumonitis (P = .428). None of the features of lung abnormalities were also associated with ICI-related pneumonitis. Multivariate logistic analysis indicated that smoking history was the only significant predictor of ICI-related pneumonitis (P = .028). Conclusion: This retrospective study did not demonstrate statistically significant association between pre-existing ILA and ICI-related pneumonitis, nor an association between radiologic features of ILA and ICI-related pneumonitis. Smoking history was independently associated with ICI-related pneumonitis. Further research is warranted for further understanding of the risk factors of ICI-related pneumonitis.
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Randomised phase II trial of trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM) versus trifluridine/tipiracil for previously treated patients with advanced gastric or esophagogastric junction adenocarcinoma (RETRIEVE study, WJOG15822G)

Takahashi N., Hara H., Nagashima K., Hirata K., Masuishi T., Matsumoto T., Kawakami H., Yamazaki K., Hironaka S., Boku N., Muro K.

BMC Cancer （BMC Cancer) 23 （ 1 ） 726 2023.12

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Background: Trifluridine/tipiracil (FTD/TPI) prolongs survival in the third- or later-line treatment for advanced gastric cancer (GC), esophagogastric junction (EGJ) adenocarcinoma, and colorectal cancer. While single-arm phase II trials showed promising outcomes of FTD/TPI plus ramucirumab (RAM) as third- or later-line treatments for advanced GC or EGJ cancer, there have been no clinical trials to directly compare FTD/TPI plus RAM with FTD/TPI monotherapy. Therefore, we have started a randomised phase II trial to evaluate the efficacy and safety of FTD/TPI plus RAM compared with FTD/TPI monotherapy as third- or later-line treatments in patients with advanced GC and EGJ adenocarcinoma. Methods: This RETREVE trial (WJOG15822G) is a prospective, open-label, randomised, multicentre phase II trial comparing FTD/TPI plus RAM versus FTD/TPI monotherapy in a third- or later-line setting. Eligibility criteria include age of > 20 years; performance status of 0 or 1; unresectable or recurrent gastric or EGJ adenocarcinoma; confirmed HER2 status; refractory or intolerant to fluoropyrimidine, taxane or irinotecan; refractory to RAM (not intolerant); and at least a measurable lesion per RECIST 1.1. FTD/TPI (35 mg/m2 twice daily, evening of day 1 to morning of day 6 and evening of day 8 to morning of day 13) was administered orally every 4 weeks, and RAM (8 mg/kg) was administered intravenously every 2 weeks. The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival, objective response rate, disease control rate, and safety. The expected hazard ratio of PFS is set as 0.7, assuming 4-month PFS rate of 27% in FTD/TPI monotherapy and 40% in FTD/TPI plus RAM. The number of subjects was 110, with a one-sided alpha error of 0.10 and power of 0.70. Discussion: This study will clarify the additional effect of RAM continuation beyond disease progression on FTD/TPI in the third- or later-line setting for patients with advanced GC or EGJ cancer. Trial registration: jRCTs041220120.
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Real-world management and outcomes of older patients with locally advanced esophageal squamous cell carcinoma: a multicenter retrospective study

Saito Y., Hamamoto Y., Hirata K., Yamasaki M., Watanabe M., Abe T., Tsubosa Y., Hamai Y., Murakami K., Bamba T., Yoshii T., Tsuda M., Watanabe M., Ueno M., Kitagawa Y.

BMC Cancer （BMC Cancer) 23 （ 1 ） 283 2023.12

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Background: Neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). Chemoradiotherapy (CRT) is an alternative treatment approach. However, both treatments are associated with toxicity, and the optimal treatment for older patients with ESCC is unknown. This study aimed to evaluate the treatment strategies and prognosis of older patients with locally advanced ESCC in a real-world setting. Methods: We retrospectively evaluated 381 older patients (≥ 65 years) with locally advanced ESCC (stage IB/II/III, excluding T4) who received anticancer therapy at 22 medical centers in Japan. Based on age, performance status (PS), and organ function, the patients were classified into two groups: clinical trial eligible and ineligible groups. Patients aged ≤ 75 years with adequate organ function and a PS of 0–1 were categorized into the eligible group. We compared the treatments and prognoses between the two groups. Results: The ineligible group had significantly shorter overall survival (OS) than the eligible group (hazard ratio [HR] for death, 1.65; 95% confidence interval [CI], 1.22–2.25; P = 0.001). The proportion of patients receiving NAC followed by surgery was significantly higher in the eligible group than in the ineligible group (P = 1.07 × 10–11), whereas the proportion of patients receiving CRT was higher in the ineligible group than in the eligible group (P = 3.09 × 10–3). Patients receiving NAC followed by surgery in the ineligible group had comparable OS to those receiving the same treatment in the eligible group (HR, 1.02; 95% CI, 0.57–1.82; P = 0.939). In contrast, patients receiving CRT in the ineligible group had significantly shorter OS than those receiving CRT in the eligible group (HR, 1.85; 95% CI, 1.02–3.37; P = 0.044). In the ineligible group, patients receiving radiation alone had comparable OS to those receiving CRT (HR, 1.13; 95% CI, 0.58–2.22; P = 0.717). Conclusions: NAC followed by surgery is justified for select older patients who can tolerate radical treatment, even if they are old or vulnerable to enrollment in clinical trials. CRT did not provide survival benefits over radiation alone in patients ineligible for clinical trials, suggesting the need to develop less-toxic CRT.
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Sunitinib-induced hyperammonemic encephalopathy in metastatic gastrointestinal stromal tumors: A case report.

Hayakawa T, Funakoshi S, Hamamoto Y, Hirata K, Kanai T

World journal of clinical cases 11 （ 31 ） 7629 - 7634 2023.11

ISSN 2307-8960
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Papers, etc., Registered in KOARA 【 Display / hide 】

Establishment of a foundation for tailor-made medicine for elderly esophageal cancer patients who are intolerant to standard therapies

Hirata, Kenrō

科学研究費補助金研究成果報告書 2019
早期胃癌におけるCD44 variant 9発現は有用な癌再発バイオマーカーとなる

Hirata, Kenro

（慶應義塾大学大学院医学研究科) 2013
早期胃癌におけるCD44 variant 9発現は有用な癌再発バイオマーカーとなる

Hirata, Kenro

（慶應義塾大学大学院医学研究科) 2013
早期胃癌におけるCD44 variant 9発現は有用な癌再発バイオマーカーとなる

Hirata, Kenro

（慶應義塾大学大学院医学研究科) 2013
The influence of H. pylori infection on iron absorption in the duodenum

Hirata, Kenro

科学研究費補助金研究成果報告書 2012

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Reviews, Commentaries, etc. 【 Display / hide 】

Gastrointestinal: Ten-millimeter advanced duodenal cancer with a gastric phenotype

Matsuura N., Kato M., Irino T., Hirata K., Yahagi N.

Journal of Gastroenterology and Hepatology (Australia) (Journal of Gastroenterology and Hepatology (Australia)) 38 ( 3 ) 347 2023.03

ISSN 08159319
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Presentations 【 Display / hide 】

Vulnerable臨床病期IB-III食道扁平上皮癌患者に対するパクリタキセル併用放射線療法の第I相試験

2021.09
,
Oral presentation (general)
Randomized phase II trial of weekly paclitaxel + ramucirumab versus weekly nab-paclitaxel + ramucirumab for unresectable advanced or recurrent gastric cancer with peritoneal dissemination refractory to first-line therapy: WJOG10617G/P-SELECT.

Kenro Hirata, Yasuo Hamamoto, Kenji Tsuchihashi, Chihiro Kondoh, Kentaro Yamazaki, Shuichi Hironaka, Masahiko Ando, Chiyo K Imamura, Kenichi Yoshimura, Kei Muro

The European Society for Medical Oncology Cancer Congress 2019,

2019.09
,
Poster presentation
咽頭メラノーシスの視認は上気道消化管新生物予測に有用である

Kenro Hirata

第15回日本臨床腫瘍学会学術集会,

2017.07
Soft palatal melanosis as a predictor for neoplasia in the upper aerodigestive tract.

Kenro Hirata

American Society of Clinical Oncology 2017,

2017.06
上気道消化管新生物予測における咽頭メラノーシスの有用性の検討

Kenro Hirata

アルコール医学生物学研究会,

2017.01
,
Oral presentation (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

がん化学療法後に増悪した根治切除不能な進行・再発食道扁平上皮癌に対するNivolumab療法におけるバイオマーカー探索を含む前向き観察研究

2021

-

Present

Joint research, Principal investigator
化学療法誘発性口腔粘膜炎における青黛軟膏の臨床開発

2021

-

Present

Joint research, Principal investigator
Vulnerable高齢食道扁平上皮癌患者に対する標準治療の確立

2020.04

-

2023.03

Research grant, Principal investigator
BRAF変異型Stage IV大腸癌に対するFOLFOXIRI+BEV療法の有効性に関する後方視的検討

2020.04

-

2021.03

Other, Principal investigator
オンライン診療を用いた緩和ケアの有用性に関する検討

2020.04

-

2021.03

Joint research, Principal investigator

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Awards 【 Display / hide 】

有吉・福岡賞

2021.06, 西日本がん研究機構（West Japan Oncology Group: WJOG）

Type of Award： Award from publisher, newspaper, foundation, etc.
J-HOPE award

2019.03, The University of Texas MD Anderson Cancer Center

Type of Award： Award from publisher, newspaper, foundation, etc.
内科学教室同窓会　松木康夫賞

2018.06
第８回 ICAT publication award

2013.12
第７回 ICAT award 最優秀賞

2012.12