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

Kentaro Yamazaki, M. Nagase, H. Tamagawa, S. Ueda, T. Tamura, K. Murata, T. Eguchi Nakajima, Eishi Baba, M. Tsuda, T. Moriwaki, T. Esaki, Y. Tsuji, K. Muro, K. Taira, T. Denda, S. Funai, K. Shinozaki, H. Yamashita, N. Sugimoto, T. Okuno & 28 others T. Nishina, M. Umeki, T. Kurimoto, T. Takayama, A. Tsuji, M. Yoshida, A. Hosokawa, Y. Shibata, K. Suyama, M. Okabe, K. Suzuki, N. Seki, K. Kawakami, M. Sato, K. Fujikawa, T. Hirashima, T. Shimura, K. Taku, T. Otsuji, F. Tamura, E. Shinozaki, K. Nakashima, H. Hara, T. Tsushima, M. Ando, S. Morita, N. Boku, I. Hyodo

研究成果: ジャーナルへの寄稿記事

50 引用 (Scopus)

抄録

Background: FOLFIRI and FOLFOX have shown equivalent efficacy for metastatic colorectal cancer (mCRC), but their comparative effectiveness is unknown when combined with bevacizumab. Patients and methods: 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 α-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. Results: 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. Conclusion: FOLFIRI plus bevacizumab was non-inferior for PFS, compared with mFOLFOX6 plus bevacizumab, as the first-line systemic treatment for mCRC. Clinical trials number: UMIN000001396.

元の言語英語
ページ(範囲)1539-1546
ページ数8
ジャーナルAnnals of Oncology
27
発行部数8
DOI
出版物ステータス出版済み - 8 1 2016

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Colorectal Neoplasms
Disease-Free Survival
Quality of Life
Confidence Intervals
Therapeutics
Febrile Neutropenia
Information Services
Venous Thromboembolism
Leukopenia
Peripheral Nervous System Diseases
Adjuvant Chemotherapy
Neutropenia
Liver Diseases
Diarrhea
Japan
Survival Rate
Bevacizumab
Clinical Trials
Safety
Survival

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

これを引用

Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G). / Yamazaki, Kentaro; Nagase, M.; Tamagawa, H.; Ueda, S.; Tamura, T.; Murata, K.; Eguchi Nakajima, T.; Baba, Eishi; Tsuda, M.; Moriwaki, T.; Esaki, T.; Tsuji, Y.; Muro, K.; Taira, K.; Denda, T.; Funai, S.; Shinozaki, K.; Yamashita, H.; Sugimoto, N.; Okuno, T.; Nishina, T.; Umeki, M.; Kurimoto, T.; Takayama, T.; Tsuji, A.; Yoshida, M.; Hosokawa, A.; Shibata, Y.; Suyama, K.; Okabe, M.; Suzuki, K.; Seki, N.; Kawakami, K.; Sato, M.; Fujikawa, K.; Hirashima, T.; Shimura, T.; Taku, K.; Otsuji, T.; Tamura, F.; Shinozaki, E.; Nakashima, K.; Hara, H.; Tsushima, T.; Ando, M.; Morita, S.; Boku, N.; Hyodo, I.

:: Annals of Oncology, 巻 27, 番号 8, 01.08.2016, p. 1539-1546.

研究成果: ジャーナルへの寄稿記事

Yamazaki, K, Nagase, M, Tamagawa, H, Ueda, S, Tamura, T, Murata, K, Eguchi Nakajima, T, Baba, E, Tsuda, M, Moriwaki, T, Esaki, T, Tsuji, Y, Muro, K, Taira, K, Denda, T, Funai, S, Shinozaki, K, Yamashita, H, Sugimoto, N, Okuno, T, Nishina, T, Umeki, M, Kurimoto, T, Takayama, T, Tsuji, A, Yoshida, M, Hosokawa, A, Shibata, Y, Suyama, K, Okabe, M, Suzuki, K, Seki, N, Kawakami, K, Sato, M, Fujikawa, K, Hirashima, T, Shimura, T, Taku, K, Otsuji, T, Tamura, F, Shinozaki, E, Nakashima, K, Hara, H, Tsushima, T, Ando, M, Morita, S, Boku, N & Hyodo, I 2016, 'Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G)', Annals of Oncology, 巻. 27, 番号 8, pp. 1539-1546. https://doi.org/10.1093/annonc/mdw206
Yamazaki, Kentaro ; Nagase, M. ; Tamagawa, H. ; Ueda, S. ; Tamura, T. ; Murata, K. ; Eguchi Nakajima, T. ; Baba, Eishi ; Tsuda, M. ; Moriwaki, T. ; Esaki, T. ; Tsuji, Y. ; Muro, K. ; Taira, K. ; Denda, T. ; Funai, S. ; Shinozaki, K. ; Yamashita, H. ; Sugimoto, N. ; Okuno, T. ; Nishina, T. ; Umeki, M. ; Kurimoto, T. ; Takayama, T. ; Tsuji, A. ; Yoshida, M. ; Hosokawa, A. ; Shibata, Y. ; Suyama, K. ; Okabe, M. ; Suzuki, K. ; Seki, N. ; Kawakami, K. ; Sato, M. ; Fujikawa, K. ; Hirashima, T. ; Shimura, T. ; Taku, K. ; Otsuji, T. ; Tamura, F. ; Shinozaki, E. ; Nakashima, K. ; Hara, H. ; Tsushima, T. ; Ando, M. ; Morita, S. ; Boku, N. ; Hyodo, I. / Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G). :: Annals of Oncology. 2016 ; 巻 27, 番号 8. pp. 1539-1546.
@article{a265705ba5f74a7394b0e242dc083234,
title = "Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G)",
abstract = "Background: FOLFIRI and FOLFOX have shown equivalent efficacy for metastatic colorectal cancer (mCRC), but their comparative effectiveness is unknown when combined with bevacizumab. Patients and methods: 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 α-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. Results: 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. Conclusion: FOLFIRI plus bevacizumab was non-inferior for PFS, compared with mFOLFOX6 plus bevacizumab, as the first-line systemic treatment for mCRC. Clinical trials number: UMIN000001396.",
author = "Kentaro Yamazaki and M. Nagase and H. Tamagawa and S. Ueda and T. Tamura and K. Murata and {Eguchi Nakajima}, T. and Eishi Baba and M. Tsuda and T. Moriwaki and T. Esaki and Y. Tsuji and K. Muro and K. Taira and T. Denda and S. Funai and K. Shinozaki and H. Yamashita and N. Sugimoto and T. Okuno and T. Nishina and M. Umeki and T. Kurimoto and T. Takayama and A. Tsuji and M. Yoshida and A. Hosokawa and Y. Shibata and K. Suyama and M. Okabe and K. Suzuki and N. Seki and K. Kawakami and M. Sato and K. Fujikawa and T. Hirashima and T. Shimura and K. Taku and T. Otsuji and F. Tamura and E. Shinozaki and K. Nakashima and H. Hara and T. Tsushima and M. Ando and S. Morita and N. Boku and I. Hyodo",
year = "2016",
month = "8",
day = "1",
doi = "10.1093/annonc/mdw206",
language = "English",
volume = "27",
pages = "1539--1546",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "8",

}

TY - JOUR

T1 - Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G)

AU - Yamazaki, Kentaro

AU - Nagase, M.

AU - Tamagawa, H.

AU - Ueda, S.

AU - Tamura, T.

AU - Murata, K.

AU - Eguchi Nakajima, T.

AU - Baba, Eishi

AU - Tsuda, M.

AU - Moriwaki, T.

AU - Esaki, T.

AU - Tsuji, Y.

AU - Muro, K.

AU - Taira, K.

AU - Denda, T.

AU - Funai, S.

AU - Shinozaki, K.

AU - Yamashita, H.

AU - Sugimoto, N.

AU - Okuno, T.

AU - Nishina, T.

AU - Umeki, M.

AU - Kurimoto, T.

AU - Takayama, T.

AU - Tsuji, A.

AU - Yoshida, M.

AU - Hosokawa, A.

AU - Shibata, Y.

AU - Suyama, K.

AU - Okabe, M.

AU - Suzuki, K.

AU - Seki, N.

AU - Kawakami, K.

AU - Sato, M.

AU - Fujikawa, K.

AU - Hirashima, T.

AU - Shimura, T.

AU - Taku, K.

AU - Otsuji, T.

AU - Tamura, F.

AU - Shinozaki, E.

AU - Nakashima, K.

AU - Hara, H.

AU - Tsushima, T.

AU - Ando, M.

AU - Morita, S.

AU - Boku, N.

AU - Hyodo, I.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Background: FOLFIRI and FOLFOX have shown equivalent efficacy for metastatic colorectal cancer (mCRC), but their comparative effectiveness is unknown when combined with bevacizumab. Patients and methods: 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 α-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. Results: 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. Conclusion: FOLFIRI plus bevacizumab was non-inferior for PFS, compared with mFOLFOX6 plus bevacizumab, as the first-line systemic treatment for mCRC. Clinical trials number: UMIN000001396.

AB - Background: FOLFIRI and FOLFOX have shown equivalent efficacy for metastatic colorectal cancer (mCRC), but their comparative effectiveness is unknown when combined with bevacizumab. Patients and methods: 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 α-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. Results: 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. Conclusion: FOLFIRI plus bevacizumab was non-inferior for PFS, compared with mFOLFOX6 plus bevacizumab, as the first-line systemic treatment for mCRC. Clinical trials number: UMIN000001396.

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JO - Annals of Oncology

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