1. Modified FOLFOXIRI plus cetuximab versus bevacizumab in RAS wild-type metastatic colorectal cancer: a randomized phase II DEEPER trial.
- Author
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Shiozawa M, Sunakawa Y, Watanabe T, Ota H, Yasui H, Yabuno T, Tei M, Kochi M, Manaka D, Ohori H, Yamaguchi T, Sagawa T, Kotaka M, Kubota Y, Sekikawa T, Nakamura M, Takeuchi M, Ichikawa W, Fujii M, and Tsuji A
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Adult, Irinotecan administration & dosage, Irinotecan therapeutic use, Progression-Free Survival, Neoplasm Metastasis, ras Proteins genetics, Prognosis, Cetuximab administration & dosage, Cetuximab therapeutic use, Colorectal Neoplasms drug therapy, Colorectal Neoplasms pathology, Colorectal Neoplasms genetics, Colorectal Neoplasms mortality, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leucovorin therapeutic use, Leucovorin administration & dosage, Bevacizumab therapeutic use, Bevacizumab administration & dosage, Fluorouracil administration & dosage, Fluorouracil therapeutic use, Camptothecin analogs & derivatives, Camptothecin therapeutic use, Camptothecin administration & dosage, Organoplatinum Compounds therapeutic use, Organoplatinum Compounds administration & dosage
- 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., Competing Interests: Competing interests: M.S. has received honoraria from Chugai Pharmaceutical Co., Ltd, Eli Lilly Japan K.K., Takeda Co., Ltd, Taiho Pharmaceutical Co., Ltd, Merck Biopharma Co., Ltd, Ono Pharmaceutical Co., Ltd, Johnson & Johnson K.K, Kaken Pharmaceutical Co., Ltd. Y.S. has received honoraria from Eli Lilly Japan K.K., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ono Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Daiichi Sankyo Co., Ltd., MSD K.K., Novartis Pharmaceuticals, Astellas Pharma Inc., Sysmex, and Guardant Health, and has also received grants from Chugai Pharmaceutical Co., Ltd. and Taiho Pharmaceutical Co., Ltd. T.Y. has received honoraria from Chugai Pharmaceutical Co., Ltd, Taiho Pharmaceutical Co., Ltd, FALCO Biosystems Ltd, Asahi Kasei Pharma Corporation Co., Ltd, Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd. M.K. has received honoraria from Chugai Pharmaceutical Co., Ltd, Eli Lilly Japan K.K., Takeda Co., Ltd, Taiho Pharmaceutical Co., Ltd, Yakult Honsha Co., Ltd. M.N. has received honoraria from Bayer Co., Ltd, Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, Eli Lilly Japan K.K., Merck Bio Pharma Co., Ltd, MSD K.K., Nihon Servier Co., Ltd, Ono Pharmaceutical Co., Ltd, Taiho Pharmaceutical Co., Ltd, Takeda Co., Ltd, and Yakult Honsha Co., Ltd. W.I. has received honoraria from Taiho Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, Takeda Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd, Merck Biopharma Co., Ltd, Yakult Honsha Co., Ltd, Bristol-Myers Squibb K.K., AstraZeneca K.K., Kyowa Kirin Co., Ltd, MSD K.K,., Nippon Kayaku Co., Ltd, and grants from Taiho Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, Shionogi & Co., Ltd, Takeda Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd, and Merck. A.T. has received honoraria from Taiho Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Ltd, Eli Lilly Japan K.K., Merck Serono Co., Ltd, Sanofi K.K., Bristol-Myers Squibb K.K. All other authors declare no competing interests., (© 2024. The Author(s).)
- Published
- 2024
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