Efficacy and safety of regorafenib dose-escalation therapy for Japanese patients with refractory metastatic colorectal cancer (RECC study)

Ishiyama, Shun; Yamada, Takeshi; Nakamura, Masato; Enomoto, Masanobu; Sugimoto, Kiichi; Yokomizo, Hajime; Kosugi, Chihiro; Ohta, Ryo; Ishimaru, Kei; Sonoda, Hiromichi; Ishibashi, Keiichiro; Kuramochi, Hidekazu; Yoshida, Yoichiro; Ichikawa, Daisuke; Hirata, Keiji; Yoshida, Hiroshi; Hashiguchi, Yojiro; Ishida, Hideyuki; Koda, Keiji; Katsumata, Kenji; Sakamoto, Kazuhiro

doi:10.1007/s10147-022-02179-9

Cited by 5 publications

(2 citation statements)

References 12 publications

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“…This is a biomarker investigation of the RECC study, which evaluated safety and efficacy of regorafenib dose-escalation therapy. The RECC study was designed as a single-arm, prospective, nonrandomized, multicentered (15 Japanese hospitals) open-label phase II trial in patients with unresectable, metastatic, or recurrent colorectal cancer that had been pathologically diagnosed as adenocarcinoma [5]. The present study was registered with the University Hospital Medical Information Network (UMIN) 000028933.…”

Section: Methodsmentioning

confidence: 99%

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Analysis of Circulating DNA to Assess Prognoses for Metastatic Colorectal Cancer Patients Treated with Regorafenib Dose-Escalation Therapy: A Retrospective, Exploratory Analysis of the RECC Trial

Ohta¹,

Yamada²,

Nakamura³

et al. 2023

Digestion

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Introduction: Regorafenib is a multi-kinase inhibitor approved for patients with metastatic colorectal cancer (mCRC) who were previously treated with standard therapies. A few reports showed the impact of KRAS mutation on therapeutic efficacy of regorafenib. Only one study reported poor prognoses for patients treated with regorafenib who had large amounts of circulating cell-free DNA (cfDNA). In the present study, we evaluated the impact of KRAS mutations in tissue or plasma and amounts of cfDNA on prognoses of mCRC patients treated with regorafenib. Method: This is a biomarker investigation of the RECC study, which evaluated efficacy of regorafenib dose-escalation therapy. Plasma samples were obtained just before initiation of treatment with regorafenib. KRAS mutations were evaluated using tissue and plasma samples. cfDNA was extracted from plasma samples and quantified. Results: Forty-five patients were enrolled in this biomarker study. Median progression-free survival (PFS) and overall survival (OS) of patients without KRAS mutations in tissues were 1.9 months (95% confidence interval [CI] 1.7–2.0) and 8.9 months (95% CI: 6.5–11.2), and those of patients with KRAS mutations were 1.4 months (95% CI: 1.3–1.5) and 6.8 months (95% CI: 5.0–8.5). Median PFS and OS of patients with plasma KRAS mutations were 1.9 months (95% CI: 1.8–1.9) and 7.0 months (95% CI: 5.3–8.7), respectively. Median PFS and OS of patients without plasma KRAS mutations were 1.7 months (95% CI: 1.1–2.3) and 8.9 months (95% CI: 6.7–11.2), respectively. Prior to administration of regorafenib, KRAS mutations were detected in 6 of 16 (37.5%) patients who had no tissue KRAS mutations. Median OS of patients with high cfDNA concentration (>median) was significantly poorer than that of patients with low cfDNA. Conclusion: KRAS mutations in the tissue or plasma have no impact on efficacy of regorafenib. KRAS emerging mutations were observed in quite a few patients. Large amounts of cfDNA may indicate poorer prognoses for patients receiving late-line regorafenib chemotherapy.

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Section: Methodsmentioning

confidence: 99%

“…This modified treatment reduces adverse events and allows continued treatment without reducing treatment efficacy, compared with conventional regorafenib therapy. We conducted a phase II study (RECC study) that included only Japanese patients and demonstrated the safety and survival benefit of regorafenib dose-escalation therapy [5].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Circulating DNA to Assess Prognoses for Metastatic Colorectal Cancer Patients Treated with Regorafenib Dose-Escalation Therapy: A Retrospective, Exploratory Analysis of the RECC Trial

Ohta¹,

Yamada²,

Nakamura³

et al. 2023

Digestion

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Bioequivalence and Pharmacokinetic Evaluation of Regorafenib Tablets in Healthy Chinese Volunteers

Wang,

Zhang,

Liu

et al. 2024

Clinical Pharm in Drug Dev

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This was a single‐center, randomized, open‐label, 2‐formulation, and 2‐cycle crossover trial conducted in 48 healthy Chinese volunteers, under fasting and fed conditions. The participants received oral doses of the test formulation (regorafenib) and reference formulation (40 mg) during each study period. Blood samples were collected before and up to 144 hours after the formulations were administered to determine changes in the pharmacokinetic parameters and adverse reactions, which were then used to evaluate bioequivalence and safety. The geometric mean ratios of maximum blood concentration, area under the plasma concentration‐time curve from time 0 to the last quantifiable concentration, and area under the plasma concentration‐time curve from time 0 to infinity for regorafenib were as follows: 94.7%, 91.4%, and 91.7%, respectively, under fasting conditions; and 94.6%, 97.7%, and 98.8%, respectively, under fed conditions. The 90% confidence intervals for the geometric mean ratios were within the 80%‐125% equivalence interval for both the fasting and fed tests. Ingesting high‐fat and high‐calorie foods increases exposure to regorafenib, leading to slower rates of absorption. The safety profiles of the 2 preparations were similar.

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Comprehensive review of signaling pathways and therapeutic targets in gastrointestinal cancers

Ji,

Chen,

et al. 2025

Critical Reviews in Oncology/Hematology

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Efficacy and safety of regorafenib dose-escalation therapy for Japanese patients with refractory metastatic colorectal cancer (RECC study)

Cited by 5 publications

References 12 publications

Analysis of Circulating DNA to Assess Prognoses for Metastatic Colorectal Cancer Patients Treated with Regorafenib Dose-Escalation Therapy: A Retrospective, Exploratory Analysis of the RECC Trial

Analysis of Circulating DNA to Assess Prognoses for Metastatic Colorectal Cancer Patients Treated with Regorafenib Dose-Escalation Therapy: A Retrospective, Exploratory Analysis of the RECC Trial

Bioequivalence and Pharmacokinetic Evaluation of Regorafenib Tablets in Healthy Chinese Volunteers

Comprehensive review of signaling pathways and therapeutic targets in gastrointestinal cancers

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