Modified FOLFOXIRI plus cetuximab versus bevacizumab in RAS wild-type metastatic colorectal cancer: a randomized phase II DEEPER trial
Abstract The clinical significance of FOLFOXIRI (5-FU, leucovorin, oxaliplatin, and irinotecan) plus anti-EGFR monoclonal antibody using cetuximab for metastatic colorectal cancer (mCRC) remains controversial. We report results from a randomized phase 2 DEEPER trial (UMIN000018217, jRCTs061180022) t...
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2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54460-2 |
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| author | Manabu Shiozawa Yu Sunakawa Takanori Watanabe Hirofumi Ota Hisateru Yasui Taichi Yabuno Mitsuyoshi Tei Mitsugu Kochi Dai Manaka Hisatsugu Ohori Tatsuro Yamaguchi Tamotsu Sagawa Masahito Kotaka Yutaro Kubota Takashi Sekikawa Masato Nakamura Masahiro Takeuchi Wataru Ichikawa Masashi Fujii Akihito Tsuji |
| author_facet | Manabu Shiozawa Yu Sunakawa Takanori Watanabe Hirofumi Ota Hisateru Yasui Taichi Yabuno Mitsuyoshi Tei Mitsugu Kochi Dai Manaka Hisatsugu Ohori Tatsuro Yamaguchi Tamotsu Sagawa Masahito Kotaka Yutaro Kubota Takashi Sekikawa Masato Nakamura Masahiro Takeuchi Wataru Ichikawa Masashi Fujii Akihito Tsuji |
| author_sort | Manabu Shiozawa |
| collection | DOAJ |
| description | Abstract The clinical significance of FOLFOXIRI (5-FU, leucovorin, oxaliplatin, and irinotecan) plus anti-EGFR monoclonal antibody using cetuximab for metastatic colorectal cancer (mCRC) remains controversial. We report results from a randomized phase 2 DEEPER trial (UMIN000018217, jRCTs061180022) to test the superiority of modified (m)-FOLFOXIRI plus weekly cetuximab over bevacizumab in patients with RAS wild-type (wt) mCRC. Primary endpoint was depth of response (DpR). Secondary endpoints included objective response rate (ORR), early tumor shrinkage (ETS) at week 8, progression-free survival (PFS), overall survival (OS), time to tumor growth (TTG), time to treatment failure (TTF), association between tumor shrinkage and prognosis, association between TTG and prognosis, R0 resection rate, and safety. In 359 enrolled patients with RAS wt mCRC, median DpR was significantly better in cetuximab (57.3% vs 46.0%, p = 0.0029); however, ORR, ETS, R0 resection rate, TTG, TTF, PFS and OS were similar between 2 treatments. There was a weak association between DpR and survival time in both treatments. The correlation between TTG and OS was slightly stronger in cetuximab. The post-hoc exploratory analysis showed that cetuximab produced greater PFS (15.3 vs 11.7 months; HR 0.68) and OS (53.6 vs 40.2 months; HR 0.54) in patients with left-sided and RAS/BRAF wt tumors. m-FOLFOXIRI plus cetuximab has clinical benefit for tumor shrinkage in RAS wt mCRC. The survival benefit for RAS/BRAF wt and left-sided mCRC needs further investigation. |
| format | Article |
| id | doaj-art-c5c30590bce046fe8b38d53091cad924 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-c5c30590bce046fe8b38d53091cad9242024-12-01T12:33:53ZengNature PortfolioNature Communications2041-17232024-11-011511910.1038/s41467-024-54460-2Modified FOLFOXIRI plus cetuximab versus bevacizumab in RAS wild-type metastatic colorectal cancer: a randomized phase II DEEPER trialManabu Shiozawa0Yu Sunakawa1Takanori Watanabe2Hirofumi Ota3Hisateru Yasui4Taichi Yabuno5Mitsuyoshi Tei6Mitsugu Kochi7Dai Manaka8Hisatsugu Ohori9Tatsuro Yamaguchi10Tamotsu Sagawa11Masahito Kotaka12Yutaro Kubota13Takashi Sekikawa14Masato Nakamura15Masahiro Takeuchi16Wataru Ichikawa17Masashi Fujii18Akihito Tsuji19Department of Gastrointestinal Surgery, Kanagawa Cancer CenterDepartment of Clinical Oncology, St. Marianna University School of MedicineDepartment of Surgery, Tokushima Municipal HospitalDepartment of Gastroenterological Surgery, Ikeda City HospitalDepartment of Medical Oncology, Kobe City Medical Center General HospitalDepartment of Gastroenterological Surgery, Yokohama Municipal Citizen’s HospitalDepartment of Surgery, Osaka Rosai HospitalDepartment of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, International University of Health and Welfare, School of MedicineDepartment of Surgery, Gastro-Intestinal Center, Kyoto Katsura HospitalDepartment of Medical Oncology, Ishinomaki Red Cross HospitalDepartment of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome HospitalDivision of Gastroenterology, National Hospital Organization Hokkaido Cancer CenterGastrointestinal Cancer Center, Sano HospitalDepartment of Clinical Oncology, Showa University HospitalDivision of Medical Oncology, Showa University Fujigaoka HospitalAizawa Comprehensive Cancer Center, Aizawa HospitalGraduate School of Mathematical Sciences, The University of TokyoDivision of Medical Oncology, Showa University Fujigaoka HospitalJapan Clinical Cancer Research OrganizationDepartment of Clinical Oncology, Faculty of Medicine, Kagawa UniversityAbstract The clinical significance of FOLFOXIRI (5-FU, leucovorin, oxaliplatin, and irinotecan) plus anti-EGFR monoclonal antibody using cetuximab for metastatic colorectal cancer (mCRC) remains controversial. We report results from a randomized phase 2 DEEPER trial (UMIN000018217, jRCTs061180022) to test the superiority of modified (m)-FOLFOXIRI plus weekly cetuximab over bevacizumab in patients with RAS wild-type (wt) mCRC. Primary endpoint was depth of response (DpR). Secondary endpoints included objective response rate (ORR), early tumor shrinkage (ETS) at week 8, progression-free survival (PFS), overall survival (OS), time to tumor growth (TTG), time to treatment failure (TTF), association between tumor shrinkage and prognosis, association between TTG and prognosis, R0 resection rate, and safety. In 359 enrolled patients with RAS wt mCRC, median DpR was significantly better in cetuximab (57.3% vs 46.0%, p = 0.0029); however, ORR, ETS, R0 resection rate, TTG, TTF, PFS and OS were similar between 2 treatments. There was a weak association between DpR and survival time in both treatments. The correlation between TTG and OS was slightly stronger in cetuximab. The post-hoc exploratory analysis showed that cetuximab produced greater PFS (15.3 vs 11.7 months; HR 0.68) and OS (53.6 vs 40.2 months; HR 0.54) in patients with left-sided and RAS/BRAF wt tumors. m-FOLFOXIRI plus cetuximab has clinical benefit for tumor shrinkage in RAS wt mCRC. The survival benefit for RAS/BRAF wt and left-sided mCRC needs further investigation.https://doi.org/10.1038/s41467-024-54460-2 |
| spellingShingle | Manabu Shiozawa Yu Sunakawa Takanori Watanabe Hirofumi Ota Hisateru Yasui Taichi Yabuno Mitsuyoshi Tei Mitsugu Kochi Dai Manaka Hisatsugu Ohori Tatsuro Yamaguchi Tamotsu Sagawa Masahito Kotaka Yutaro Kubota Takashi Sekikawa Masato Nakamura Masahiro Takeuchi Wataru Ichikawa Masashi Fujii Akihito Tsuji Modified FOLFOXIRI plus cetuximab versus bevacizumab in RAS wild-type metastatic colorectal cancer: a randomized phase II DEEPER trial Nature Communications |
| title | Modified FOLFOXIRI plus cetuximab versus bevacizumab in RAS wild-type metastatic colorectal cancer: a randomized phase II DEEPER trial |
| title_full | Modified FOLFOXIRI plus cetuximab versus bevacizumab in RAS wild-type metastatic colorectal cancer: a randomized phase II DEEPER trial |
| title_fullStr | Modified FOLFOXIRI plus cetuximab versus bevacizumab in RAS wild-type metastatic colorectal cancer: a randomized phase II DEEPER trial |
| title_full_unstemmed | Modified FOLFOXIRI plus cetuximab versus bevacizumab in RAS wild-type metastatic colorectal cancer: a randomized phase II DEEPER trial |
| title_short | Modified FOLFOXIRI plus cetuximab versus bevacizumab in RAS wild-type metastatic colorectal cancer: a randomized phase II DEEPER trial |
| title_sort | modified folfoxiri plus cetuximab versus bevacizumab in ras wild type metastatic colorectal cancer a randomized phase ii deeper trial |
| url | https://doi.org/10.1038/s41467-024-54460-2 |
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