Evidence map›Paper›PMID 39587053›Full record

Trial reportNature communications2024

Modified FOLFOXIRI plus cetuximab versus bevacizumab in RAS wild-type metastatic colorectal cancer: a randomized phase II DEEPER trial.

Manabu Shiozawa, Yu Sunakawa, Takanori Watanabe, Hirofumi Ota, Hisateru Yasui, Taichi Yabuno, Mitsuyoshi Tei, Mitsugu Kochi, Dai Manaka, Hisatsugu Ohori and 10 more

Abstract readClinical Trial, Phase IIRandomized Controlled TrialMulticenter Study
In one paragraph

Trial report in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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  3. Upfront Modified FOLFOXIRI Plus Panitumumab forJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Manabu Shiozawa *Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan.
Yu Sunakawa *Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan. y.suna0825@gmail.com.ORCID 0000-0002-0163-7543
Takanori WatanabeDepartment of Surgery, Tokushima Municipal Hospital, Tokushima, Japan.
Hirofumi OtaDepartment of Gastroenterological Surgery, Ikeda City Hospital, Ikeda, Japan.
Hisateru YasuiDepartment of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan.
Taichi YabunoDepartment of Gastroenterological Surgery, Yokohama Municipal Citizen's Hospital, Yokohama, Japan.
Mitsuyoshi TeiDepartment of Surgery, Osaka Rosai Hospital, Osaka, Japan.
Mitsugu KochiDepartment of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, International University of Health and Welfare, School of Medicine, Otawara, Japan.
Dai ManakaDepartment of Surgery, Gastro-Intestinal Center, Kyoto Katsura Hospital, Kyoto, Japan.
Hisatsugu OhoriDepartment of Medical Oncology, Ishinomaki Red Cross Hospital, Ishinomaki, Japan.
Tatsuro YamaguchiDepartment of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.ORCID 0000-0001-8454-1995
Tamotsu SagawaDivision of Gastroenterology, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan.
Masahito KotakaGastrointestinal Cancer Center, Sano Hospital, Kobe, Japan.
Yutaro KubotaDepartment of Clinical Oncology, Showa University Hospital, Tokyo, Japan.
Takashi SekikawaDivision of Medical Oncology, Showa University Fujigaoka Hospital, Yokohama, Japan.
Masato NakamuraAizawa Comprehensive Cancer Center, Aizawa Hospital, Matsumoto, Japan.
Masahiro TakeuchiGraduate School of Mathematical Sciences, The University of Tokyo, Tokyo, Japan.
Wataru IchikawaDivision of Medical Oncology, Showa University Fujigaoka Hospital, Yokohama, Japan.
Masashi FujiiJapan Clinical Cancer Research Organization, Tokyo, Japan.
Akihito TsujiDepartment of Clinical Oncology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBevacizumabCamptothecinCetuximabColorectal NeoplasmsFluorouracilLeucovorinOrganoplatinum CompoundsAdultAgedFemaleHumansIrinotecanMaleMiddle AgedNeoplasm MetastasisBevacizumabCamptothecinCetuximabFluorouracilIrinotecanLeucovorinOrganoplatinum Compoundsras Proteins

Identifiers

PMID39587053
PMCPMC11589592

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.