Evidence map›Paper›PMID 42159904›Full record

ArticleTargeted oncology2026

Plasma Biomarkers Associated with Clinical Outcomes of FOLFIRI Plus Ramucirumab in RAS Wild-Type Metastatic Colorectal Cancer: The JACCRO CC-16AR Trial.

Yu Sunakawa, Hisateru Yasui, Manabu Shiozawa, Hiroyuki Takeda, Naoya Akazawa, Tamotsu Sagawa, Kazuhiro Shiraishi, Takahisa Kyogoku, Takashi Mine, Yasuhiro Yuasa and 12 more

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Article in Targeted oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

22 authors.

Yu SunakawaDepartment of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan. y.suna0825@gmail.com.ORCID http://orcid.org/0000-0002-0163-7543
Hisateru YasuiDepartment of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan.
Manabu ShiozawaDepartment of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan.
Hiroyuki TakedaDepartment of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.
Naoya AkazawaDepartment of Gastroenterological Surgery, Sendai City Medical Center Sendai Open Hospital, Sendai, Japan.
Tamotsu SagawaDepartment of Gastroenterology, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan.
Kazuhiro ShiraishiDepartment of Medical Oncology, NHO Nagoya Medical Center, Nagoya, Japan.
Takahisa KyogokuDepartment of Surgery, Kobe City Nishi-Kobe Medical Center, Kobe, Japan.
Takashi MineDepartment of Clinical Oncology, Nagasaki Harbor Medical Center, Nagasaki, Japan.
Yasuhiro YuasaDepartment of Gastrointestinal Surgery, Tokushima Red Cross Hospital, Tokushima, Japan.
Takanori WatanabeDepartment of Surgery, Japanese Red Cross Society Himeji Hospital, Himeji, Japan.
Tatsuya KinjoDivision of Digestive and General Surgery, University of the Ryukyus, Ginowan, Japan.
Yoshihiro OkitaDepartment of Clinical Oncology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Hiroyuki OkuyamaDepartment of Clinical Oncology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Satoshi YukiDepartment of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan.
Koki MiyakawaSysmex Corporation, Kobe, Japan.
Ayana KobaraSysmex Corporation, Kobe, Japan.
Shoko YanakaG&G SCIENCE CO., LTD., Fukushima, Japan.
Yukiko AbeG&G SCIENCE CO., LTD., Fukushima, Japan.
Wataru IchikawaDivision of Medical Oncology, Showa Medical 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

backgroundSecond-line FOLFIRI plus ramucirumab (RAM) is one of standard treatments for metastatic colorectal cancer (mCRC) following progression on anti-EGFR therapy in RAS wild-type tumors. However, biomarkers for RAM efficacy remain unclear.

objectiveWe conducted a translational analysis to evaluate the association of plasma biomarkers, including angiogenesis-related factors (AFs) and RAS mutations in circulating tumor DNA (ctDNA), with clinical outcomes.

methodsThis biomarker study was embedded within the JACCRO CC-16 trial, which enrolled patients with mCRC with RAS wild-type tumors receiving FOLFIRI plus RAM after anti-EGFR therapy. Plasma samples were collected at baseline, day 15, and post-treatment. RAS status in ctDNA was analyzed using BEAMing digital PCR; AFs were assessed using Luminex multiplex assay. Associations with progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were analyzed.

resultsAmong 41 evaluable patients with RAS wild-type tumors, RAS mutations were detected in ctDNA at pretreatment in 44%. Patients without RAS mutations had significantly longer OS (28.1 versus 14.8 months; HR 0.30, p = 0.0008) and higher ORR (14.3% versus 5.6%). Elevated baseline interleukin-8 (IL-8) was associated with poorer OS (16.5 versus 32.2 months; HR 1.99, p = 0.049). IL-8 levels were significantly higher in patients with RAS mutations.

conclusionRAS mutations in ctDNA and elevated IL-8 levels prior to second-line FOLFIRI plus RAM were associated with worse prognosis in mCRC. Moreover, our study demonstrated a significant association between RAS mutations and high IL-8 levels in this setting, suggesting a potential molecular-inflammatory interplay that contributes to resistance to VEGFR2 blockade.

Indexed as

Antibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCamptothecinColorectal NeoplasmsAdultAgedFemaleFluorouracilHumansLeucovorinMaleMiddle AgedNeoplasm MetastasisRamucirumabAntibodies, Monoclonal, HumanizedBiomarkers, TumorCamptothecinFluorouracilLeucovorinRamucirumab

Identifiers

PMID42159904

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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.