Evidence map›Paper›PMID 34764486›Full record

Trial reportNature medicine2021

Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial.

Yoshiaki Nakamura, Wataru Okamoto, Takeshi Kato, Taito Esaki, Ken Kato, Yoshito Komatsu, Satoshi Yuki, Toshiki Masuishi, Tomohiro Nishina, Hiromichi Ebi and 17 more

Open access · hybridAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
145citing papers in PubMed, 2 pooled it
15.7field-weighted citation impact, top 1% of its field
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

145 citing papers in PubMed, 2 syntheses or guidelines pooled it, 235 citations in OpenAlex.

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  5. Trastuzumab Plus Pertuzumab Versus Cetuximab Plus Irinotecan in Patients WithJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025
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  16. Pertuzumab Plus Trastuzumab for Treatment-RefractoryJCO clinical cancer informatics · 2022
    Trial
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85 more citing papers are in PubMed but not listed here.

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

27 authors at 9 institutions in 2 countries.

Yoshiaki Nakamura *Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Wataru Okamoto *Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Takeshi KatoDepartment of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan.
Taito EsakiDepartment of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
Ken KatoDepartment of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.ORCID http://orcid.org/0000-0002-1733-5072
Yoshito KomatsuDepartment of Cancer Center, Hokkaido University Hospital, Sapporo, Japan.ORCID http://orcid.org/0000-0002-1570-6802
Satoshi YukiDepartment of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan.
Toshiki MasuishiDepartment of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Tomohiro NishinaGastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
Hiromichi EbiDivision of Molecular Therapeutics, Aichi Cancer Center Research Institute, Nagoya, Japan.ORCID http://orcid.org/0000-0003-3155-7576
Kentaro SawadaDepartment of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Hiroya TaniguchiDepartment of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Nozomu FuseClinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.
Shogo NomuraClinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.
Makoto FukuiClinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.
Seiko MatsudaClinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.
Yasutoshi SakamotoTranslational Research Support Section, National Cancer Center Hospital East, Kashiwa, Japan.
Hiroshi UchigataTranslational Research Support Section, National Cancer Center Hospital East, Kashiwa, Japan.
Kana KitajimaTranslational Research Support Section, National Cancer Center Hospital East, Kashiwa, Japan.
Naomi KuramotoTranslational Research Support Section, National Cancer Center Hospital East, Kashiwa, Japan.
Takashi AsakawaChugai Pharmaceutical Co., Ltd, Tokyo, Japan.
Steve OlsenClinical and Medical Affairs, Guardant Health AMEA, Redwood City CA, USA.
Justin I OdegaardClinical Development, Guardant Health, Redwood City CA, USA.
Akihiro SatoClinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.
Satoshi FujiiDivision of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan.
Atsushi OhtsuDepartment of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Takayuki YoshinoDepartment of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. tyoshino@east.ncc.go.jp.ORCID http://orcid.org/0000-0002-0489-4756
National Cancer Center Hospital East · JPAichi Cancer Center · JPGuardant (United States) · USHokkaido University Hospital · JPHiroshima University Hospital · JPKushiro Rosai Hospital · JPNational Hospital Organization Kyushu Cancer Center · JPOsaka National Hospital · JPShikoku Cancer Center · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The applicability of circulating tumor DNA (ctDNA) genotyping to inform enrollment of patients with cancer in clinical trials has not been established. We conducted a phase 2 trial to evaluate the efficacy of pertuzumab plus trastuzumab for metastatic colorectal cancer (mCRC), with human epidermal growth factor receptor 2 (HER2) amplification prospectively confirmed by tumor tissue or ctDNA analysis ( UMIN000027887 ). HER2 amplification was confirmed in tissue and/or ctDNA in 30 patients with mCRC. The study met the primary endpoint with a confirmed objective response rate of 30% in 27 tissue-positive patients and 28% in 25 ctDNA-positive patients, as compared to an objective response rate of 0% in a matched real-world reference population treated with standard-of-care salvage therapy. Post hoc exploratory analyses revealed that baseline ctDNA genotyping of HER2 copy number and concurrent oncogenic alterations adjusted for tumor fraction stratified patients according to efficacy with similar accuracy to tissue genotyping. Decreased ctDNA fraction 3 weeks after treatment initiation associated with therapeutic response. Pertuzumab plus trastuzumab showed similar efficacy in patients with mCRC with HER2 amplification in tissue or ctDNA, showing that ctDNA genotyping can identify patients who benefit from dual-HER2 blockade as well as monitor treatment response. These findings warrant further use of ctDNA genotyping in clinical trials for HER2-amplified mCRC, which might especially benefit patients in first-line treatment.

Indexed as

AdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsCirculating Tumor DNAColorectal NeoplasmsErb-b2 Receptor Tyrosine KinasesFemaleGene DosageGenotyping TechniquesHumansMaleMiddle AgedProspective StudiesAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalCirculating Tumor DNAERBB2 protein, humanErb-b2 Receptor Tyrosine KinasespertuzumabTrastuzumab

Identifiers

PMID34764486
PMCPMC8604726
OpenAlexW3212458558

What OpenQuestion holds

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LicenceCC BY
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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.