Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G)

被引：205

作者：

Yamazaki, K. ^{[1
]}

Nagase, M. ^{[2
]}

Tamagawa, H. ^{[3
]}

Ueda, S. ^{[4
]}

Tamura, T. ^{[5
]}

Murata, K. ^{[6
]}

Nakajima, T. Eguchi ^{[7
]}

Baba, E. ^{[8
]}

Tsuda, M. ^{[9
]}

Moriwaki, T. ^{[10
]}

Esaki, T. ^{[11
]}

Tsuji, Y. ^{[12
]}

Muro, K. ^{[13
]}

Taira, K. ^{[14
]}

Denda, T. ^{[15
]}

Funai, S. ^{[16
]}

Shinozaki, K. ^{[17
]}

Yamashita, H. ^{[18
]}

Sugimoto, N. ^{[19
]}

Okuno, T. ^{[20
]}

Nishina, T. ^{[21
]}

Umeki, M. ^{[22
]}

Kurimoto, T. ^{[23
]}

Takayama, T. ^{[24
]}

Tsuji, A. ^{[25
]}

Yoshida, M. ^{[26
]}

Hosokawa, A. ^{[27
]}

Shibata, Y. ^{[28
]}

Suyama, K. ^{[29
]}

Okabe, M. ^{[30
]}

Suzuki, K. ^{[31
]}

Seki, N. ^{[32
]}

Kawakami, K. ^{[33
]}

Sato, M. ^{[34
]}

Fujikawa, K. ^{[35
]}

Hirashima, T. ^{[36
]}

Shimura, T. ^{[37
]}

Taku, K. ^{[38
]}

Otsuji, T. ^{[39
]}

Tamura, F. ^{[40
]}

Shinozaki, E. ^{[41
]}

Nakashima, K. ^{[42
]}

Hara, H. ^{[43
]}

Tsushima, T. ^{[1
]}

Ando, M. ^{[44
]}

Morita, S. ^{[45
]}

Boku, N. ^{[7
]}

Hyodo, I. ^{[10
]}

机构：

[1] Shizuoka Canc Ctr, Div Gastrointestinal Oncol, 1007 Shimonagakubo, Nagaizumi, Shizuoka 4118777, Japan

[2] Jichi Med Univ, Dept Clin Oncol, Shimotsuke, Japan

[3] Osaka Gen Med Ctr, Dept Surg, Osaka, Japan

[4] Kinki Univ, Dept Med Oncol, Fac Med, Higashiosaka, Osaka, Japan

[5] Kinki Univ, Dept Med Oncol, Nara Hosp, Fac Med, Ikoma, Japan

[6] Suita Municipal Hosp, Dept Surg, Suita, Osaka, Japan

[7] St Marianna Univ, Dept Clin Oncol, Sch Med, Kawasaki, Kanagawa, Japan

[8] Kyushu Univ, Dept Comprehens Clin Oncol, Fac Med Sci, Fukuoka, Japan

[9] Hyogo Canc Ctr, Dept Gastroenterol Oncol, Akashi, Hyogo, Japan

[10] Univ Tsukuba, Div Gastroenterol, Tsukuba, Ibaraki, Japan

[11] Natl Hosp Org Kyushu Canc Ctr, Dept Gastrointestinal & Med Oncol, Fukuoka, Japan

[12] Tonan Hosp, Dept Med Oncol, Sapporo, Hokkaido, Japan

[13] Aichi Canc Ctr Hosp, Dept Clin Oncol, Nagoya, Aichi, Japan

[14] Osaka City Gen Hosp, Clin Oncol, Osaka, Japan

[15] Chiba Canc Ctr, Div Gastroenterol, Chiba, Japan

[16] Kinki Univ, Dept Surg, Sakai Hosp, Fac Med, Sakai, Osaka, Japan

[17] Hiroshima Prefectural Hosp, Div Clin Oncol, Hiroshima, Japan

[18] Okayama Med Ctr, Dept Gastroenterol & Hepatol, Okayama, Japan

[19] Osaka Med Ctr Canc & Cardiovasc Dis, Dept Clin Oncol, Osaka, Japan

[20] Kobe Univ, Dept Internal Med, Div Gastroenterol, Grad Sch Med, Kobe, Hyogo, Japan

[21] Natl Hosp Org Shikoku Canc Ctr, Dept Gastrointestinal Med Oncol, Matsuyama, Japan

[22] Hyogo Prefectural Awaji Med Ctr, Dept Surg, Sumoto, Japan

[23] Nagoya Kyoritsu Hosp, Dept Gastrointestinal Oncol, Nagoya, Aichi, Japan

[24] Univ Tokushima, Dept Gastroenterol & Oncol, Grad Sch, Tokushima, Japan

[25] Kochi Hlth Sci Ctr, Dept Med Oncol, Kochi, Japan

[26] Osaka Med Coll Hosp, Div Canc Chemotherapy Ctr, Takatsuki, Osaka, Japan

[27] Toyama Univ, Dept Gastroenterol & Hematol, Fac Med, Toyama, Japan

[28] Miyazaki Prefectural Miyazaki Hosp, Dept Chemotherapy, Miyazaki, Japan

[29] Toranomon Gen Hosp, Dept Med Oncol, Tokyo, Japan

[30] Kurashiki Cent Hosp, Dept Surg, Kurashiki, Okayama, Japan

[31] Kushiro City Gen Hosp, Dept Gastroenterol, Kushiro, Hokkaido, Japan

[32] Teikyo Univ, Dept Internal Med, Div Med Oncol, Sch Med, Tokyo, Japan

[33] Muroran City Gen Hosp, Dept Gastroenterol, Muroran, Hokkaido, Japan

[34] Ryuugasaki Saiseikai Hosp, Dept Gastroenterol & Hepatol, Ryugasaki, Japan

[35] Hokkaido Canc Ctr, Dept Gastroenterol, Sapporo, Hokkaido, Japan

[36] Osaka Prefectural Med Ctr Resp & Allerg Dis, Dept Thorac Malignancy, Habikino, Japan

[37] Nagoya City Univ, Dept Gastroenterol & Metab, Grad Sch Med Sci, Nagoya, Aichi, Japan

[38] Shizuoka Prefectural Gen Hosp, Div Med Oncol, Shizuoka, Japan

[39] Dongo Hosp, Dept Gastroenterol, Yamatotakada, Japan

[40] Kumamoto Reg Med Ctr, Dept Gastroenterol, Kumamoto, Japan

[41] Canc Inst Hosp JFCR, Dept Gastroenterol, Tokyo, Japan

[42] Miyazaki Univ, Dept Internal Med 1, Fac Med, Miyazaki, Japan

[43] Saitama Canc Ctr, Dept Gastroenterol, Saitama, Japan

[44] Nagoya Univ Hosp, Ctr Adv Med & Clin Res, Nagoya, Aichi, Japan

[45] Kyoto Univ, Dept Biomed Stat & Bioinformat, Grad Sch Med, Kyoto, Japan

来源：

ANNALS OF ONCOLOGY | 2016年 / 27卷 / 08期

关键词：

irinotecan; oxaliplatin; bevacizumab; colorectal cancer; phase III study; CONTROLLED-TRIAL; OPEN-LABEL; FLUOROURACIL; OXALIPLATIN; LEUCOVORIN; IRINOTECAN; CHEMOTHERAPY; COMBINATION; CETUXIMAB; THERAPY;

D O I：

10.1093/annonc/mdw206

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

This randomized phase III trial compared FOLFIRI plus bevacizumab with mFOLFOX6 plus bevacizumab as the first-line treatment for patients with metastatic colorectal cancer. This direct comparative phase III trial demonstrated that FOLFIRI plus bevacizumab was non-inferior to mFOLFOX6 plus bevacizumab in terms of progression-free survival, and was associated with favorable quality of life profiles.FOLFIRI and FOLFOX have shown equivalent efficacy for metastatic colorectal cancer (mCRC), but their comparative effectiveness is unknown when combined with bevacizumab. WJOG4407G was a randomized, open-label, phase III trial conducted in Japan. Patients with previously untreated mCRC were randomized 1:1 to receive either FOLFIRI plus bevacizumab (FOLFIRI + Bev) or mFOLFOX6 plus bevacizumab (mFOLFOX6 + Bev), stratified by institution, adjuvant chemotherapy, and liver-limited disease. The primary end point was non-inferiority of FOLFIRI + Bev to mFOLFOX6 + Bev in progression-free survival (PFS), with an expected hazard ratio (HR) of 0.9 and non-inferiority margin of 1.25 (power 0.85, one-sided alpha-error 0.025). The secondary end points were response rate (RR), overall survival (OS), safety, and quality of life (QoL) during 18 months. This trial is registered to the University Hospital Medical Information Network, number UMIN000001396. Among 402 patients enrolled from September 2008 to January 2012, 395 patients were eligible for efficacy analysis. The median PFS for FOLFIRI + Bev (n = 197) and mFOLFOX6 + Bev (n = 198) were 12.1 and 10.7 months, respectively [HR, 0.905; 95% confidence interval (CI) 0.723-1.133; P = 0.003 for non-inferiority]. The median OS for FOLFIRI + Bev and mFOLFOX6 + Bev were 31.4 and 30.1 months, respectively (HR, 0.990; 95% CI 0.785-1.249). The best overall RRs were 64% for FOLFIRI + Bev and 62% for mFOLFOX6 + Bev. The common grade 3 or higher adverse events were leukopenia (11% in FOLFIRI + Bev/5% in mFOLFOX6 + Bev), neutropenia (46%/35%), diarrhea (9%/5%), febrile neutropenia (5%/2%), peripheral neuropathy (0%/22%), and venous thromboembolism (6%/2%). The QoL assessed by FACT-C (TOI-PFC) and FACT/GOG-Ntx was favorable for FOLFIRI + Bev during 18 months. FOLFIRI plus bevacizumab was non-inferior for PFS, compared with mFOLFOX6 plus bevacizumab, as the first-line systemic treatment for mCRC. UMIN000001396.

引用

页码：1539 / 1546

页数：8

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