Phase II study of trifluridine/tipiracil plus bevacizumab by RAS mutation status in patients with metastatic colorectal cancer refractory to standard therapies: JFMC51-1702-C7

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T. Takahashi¹  K. Yamazaki²  E. Oki³  M. Shiozawa⁴  K. Mitsugi⁵  A. Makiyama⁶  M. Nakamura⁷  H. Ojima⁸  Y. Kagawa⁹  N. Matsuhashi¹  H. Okuda^1,10  M. Asayama^1,11  Y. Yuasa^1,12  Y. Shimada^1,13  D. Manaka^1,14  J. Watanabe^1,15  K. Oba^1,16  T. Yoshino^1,17  K. Yoshida¹  Y. Maehara^1,18 

[1] Department of Digestive Surgery, Gifu University Hospital;Division of Gastrointestinal Oncology, Shizuoka Cancer Center;Department of Surgery and Science, Kyushu University;Department of Gastrointestinal Surgery, Kanagawa Cancer Center;Department of Medical Oncology, Hamanomachi Hospital;Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital;Department of Gastroenterology, Sapporo City General Hospital;Department of Gastroenterological Surgery, Gunma Prefectural Cancer Center;Department of Surgery, Kansai Rosai Hospital;Department of Medical Oncology, Keiyukai Sapporo Hospital;Department of Gastroenterology, Saitama Cancer Center;Department of Gastrointestinal Surgery, Tokushima Red Cross Hospital;Division of Clinical Oncology, Kochi Health Sciences Center;Department of Surgery, Kyoto Katsura Hospital;Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center;Department of Interfaculty and Initiatives in Information Studies, University of Tokyo;Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East;Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers

关键词: metastatic colorectal cancer;    bevacizumab;    trifluridine/tipiracil;    RAS mutation status;    JFMC51-1702-C7 trial;   

DOI  :  10.1016/j.esmoop.2021.100093

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Although the efficacy of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) against metastatic colorectal cancer (mCRC) has been demonstrated, little is known about its effectiveness upon disease stratification by RAS mutations. In this phase II study, we investigated the efficacy and safety profiles of FTD/TPI in mCRC according to RAS mutation status.Patients and methods Eligible patients were mCRC refractory or intolerant to all standard therapies other than FTD/TPI and regorafenib. Patients received 4-week cycles of treatment with FTD/TPI (35 mg/m2, twice daily, days 1-5 and 8-12) and bevacizumab (5 mg/kg, days 1 and 15). The primary endpoint was disease control rate (DCR). The null hypothesis of DCR in both RAS wild-type (WT) and mutant (MUT) cohorts was 44%, assuming a one-sided significance level of 5.0%. The necessary sample size was estimated to be 49 patients (target sample size: 50 patients) for each cohort.Results Between January and September 2018, 102 patients were enrolled, and 97 patients fulfilled the eligibility criteria (48 in the RAS WT cohort and 49 in the RAS MUT cohort). DCRs in the RAS WT and MUT cohort were 66.7% [90% confidence interval (CI), 53.9%-77.8%, P = 0.0013] and 55.1% (90% CI, 42.4%-67.3%, P = 0.0780), respectively. The median progression-free survival (PFS) and overall survival (OS) were 3.8 and 9.3 months, respectively, in the RAS WT cohort and 3.5 and 8.4 months, respectively, in the RAS MUT cohort. The most common grade 3 or higher adverse event in both cohorts was neutropenia (46% in the RAS WT cohort and 62% in the RAS MUT cohort), without unexpected safety signals.Conclusions FTD/TPI plus bevacizumab showed promising activity with an acceptable safety profile for pretreated mCRC, regardless of RAS mutation status, although the efficacy outcomes tended to be better in RAS WT.

【 授权许可】

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