Long-Term Survival Outcomes of Modified-FOLFOXIRI Plus Cetuximab Versus Bevacizumab in RAS / BRAF Wild-Type Metastatic Colorectal Cancer: Final Analysis of the DEEPER Trial
The randomized phase II DEEPER trial (jRCTs061180022) previously reported superior depth of response with modified 5-fluorouracil, leucovorin, oxaliplatin and irinotecan (m-FOLFOXIRI) plus cetuximab versus bevacizumab in patients with RAS wild-type metastatic colorectal cancer (mCRC). Here, we report updated final survival outcomes and exploratory subgroup analyses focusing on RAS / BRAF wild-type and left-sided tumors. Final overall survival (OS) and progression-free survival (PFS) were analyzed in the per-protocol set (PPS) with exploratory subgroup analyses according to the presence of liver-limited disease and sex, using extended follow-up data. There were no differences in PFS and OS in the PPS. In patients with RAS / BRAF wild-type and left-sided tumors, median PFS was longer with cetuximab than with bevacizumab (14.8 v 11.9 months; hazard ratio [HR], 0.71 [95% CI, 0.52 to 0.97]; P = .029). The median OS was 50.2 months for cetuximab and 40.2 months for bevacizumab (HR, 0.74 [95% CI, 0.53 to 1.05]). In the exploratory analyses, cetuximab-based therapy was associated with longer OS in male patients (HR, 0.59; P = .016) and in patients with extrahepatic disease (HR, 0.60; P = .014). In conclusion, the DEEPER trial suggests that m-FOLFOXIRI plus cetuximab achieves superior tumor shrinkage and may be associated with favorable outcomes in selected patients with RAS / BRAF wild-type and left-sided mCRC, with exploratory signals of benefit in male patients and those with extrahepatic disease.
Authors
- Yutaro Kubota (ORCID: https://orcid.org/0000-0002-2917-8764)
- Wataru Ichikawa (ORCID: https://orcid.org/0000-0001-5543-4488)
- Yu Sunakawa (ORCID: https://orcid.org/0000-0002-0163-7543)
- Hisatsugu Ohori
- Dai Manaka (ORCID: https://orcid.org/0000-0002-7033-4298)
- Tatsuro Yamaguchi (ORCID: https://orcid.org/0000-0001-8454-1995)
- Masahito Kotaka (ORCID: https://orcid.org/0000-0001-5976-613X)
- Akihito Tsuji (ORCID: https://orcid.org/0000-0003-4034-1945)
- Hisateru Yasui (ORCID: https://orcid.org/0000-0001-5563-5802)
- Taichi Yabuno
- Hirofumi Ota (ORCID: https://orcid.org/0000-0002-8659-6700)
- Mitsuyoshi Tei (ORCID: https://orcid.org/0000-0003-0236-3641)
- Mitsugu Kochi (ORCID: https://orcid.org/0000-0003-2781-4947)
- Tamotsu Sagawa
- Takashi Sekikawa
- Masahiro Takeuchi
- Takanori Watanabe
- Masashi Fujii
- Manabu Shiozawa
- Masato Nakamura
Institutions
- Nihon University (JP)
- SHOWA Medical University (JP)
- St. Marianna University School of Medicine (JP)
- Kagawa University (JP)
- Kanagawa Prefectural Hospital Organization (JP)
- Tokyo Metropolitan Komagome Hospital (JP)
- Ikeda Municipal Hospital (JP)
- National Hospital Organization Hokkaido Medical Center (JP)
- Osaka Rosai Hospital (JP)
- SOUSEIKAI Global Clinical Research Center (JP)
- Yokohama Municipal Citizen's Hospital (JP)
- Kyoto Katsura Hospital (JP)
- Japan Clinical Cancer Research Organization (JP)
- Aizawa Hospital (JP)
- SHOWA Medical University Fujigaoka Hospital (JP)
- Tokushima Municipal Hospital (JP)
- Kobe City Medical Center General Hospital (JP)
- Sapporo National Hospital (JP)
- Kanagawa Cancer Center
- The University of Tokyo (JP)
Publication Details
- Journal
- Journal of Clinical Oncology
- Published
- 2026-08-27
- DOI
- https://doi.org/10.1200/jco-26-00355
- Primary Topic
- Colorectal Cancer Treatments and Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Amgen
- GlaxoSmithKline
- Merck KGaA
- Astellas Pharma
- Ono Pharmaceutical
- Daiichi Sankyo Europe