Evidence map›Paper›PMID 34109122›Full record

ArticleFrontiers in oncology2021

Early Exanthema Upon Vemurafenib Plus Cobimetinib Is Associated With a Favorable Treatment Outcome in Metastatic Melanoma: A Retrospective Multicenter DeCOG Study.

Katharina C Kähler, Ralf Gutzmer, Friedegrund Meier, Lisa Zimmer, Markus Heppt, Anja Gesierich, Kai-Martin Thoms, Jochen Utikal, Jessica C Hassel, Carmen Loquai and 11 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 52% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
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

21 authors at 15 institutions in 1 country.

Katharina C KählerDepartment of Dermatology, University Hospital Schleswig-Holstein (UKSH), Kiel, Germany.
Ralf GutzmerDepartment of Dermatology, University Hospital Hannover, Hannover, Germany.
Friedegrund MeierSkin Cancer Center, National Center for Tumor Diseases, University Cancer Centre Dresden, Dresden, Germany.
Lisa ZimmerDepartment of Dermatology, University Hospital Essen, German Cancer Consortium (DKTK), Essen, Germany.
Markus HepptDepartment of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Anja GesierichDepartment of Dermatology, University Hospital Würzburg, Würzburg, Germany.
Kai-Martin ThomsDepartment of Dermatology, University Medical Center Göttingen, Göttingen, Germany.
Jochen UtikalSkin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Jessica C HasselDepartment of Dermatology, University Hospital Heidelberg, Heidelberg, Germany.
Carmen LoquaiDepartment of Dermatology, University Hospital Mainz, Mainz, Germany.
Claudia PföhlerDepartment of Dermatology, University Hospital Homburg, Homburg, Germany.
Lucie HeinzerlingDepartment of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Martin KaatzDepartment of Dermatology, SRH Waldklinikum, Gera, Germany.
Daniela GöppnerDepartment of Dermatology, University Hospital Giessen, Gießen, Germany.
Annette PflugfelderDepartment of Dermatology, University Hospital Tübingen, Tübingen, Germany.
Ann-Sophie BohneDepartment of Dermatology, University Hospital Schleswig-Holstein (UKSH), Kiel, Germany.
Imke SatzgerDepartment of Dermatology, University Hospital Hannover, Hannover, Germany.
Lydia ReinhardtSkin Cancer Center, National Center for Tumor Diseases, University Cancer Centre Dresden, Dresden, Germany.
Jan-Malte PlackeDepartment of Dermatology, University Hospital Essen, German Cancer Consortium (DKTK), Essen, Germany.
Dirk SchadendorfDepartment of Dermatology, University Hospital Essen, German Cancer Consortium (DKTK), Essen, Germany.
Selma UgurelDepartment of Dermatology, University Hospital Essen, German Cancer Consortium (DKTK), Essen, Germany.
Deutschen Konsortium für Translationale Krebsforschung · DEEssen University Hospital · DEUniversity Hospital Heidelberg · DEFriedrich-Alexander-Universität Erlangen-Nürnberg · DEJohannes Gutenberg University Mainz · DESRH Wald-Klinikum Gera · DETechnische Universität Dresden · DEUniversitätsklinikum Erlangen · DEUniversitätsklinikum Gießen und Marburg · DEUniversitätsklinikum Würzburg · DEUniversitätsmedizin Göttingen · DEUniversity Children's Hospital Tübingen · DEUniversity Hospital Carl Gustav Carus · DEUniversity Hospital Schleswig-Holstein · DEUniversity of Lübeck · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe combination of BRAF and MEK inhibitors has become standard of care in the treatment of metastatic BRAF V600-mutated melanoma. Clinical factors for an early prediction of tumor response are rare. The present study investigated the association between the development of an early exanthema induced by vemurafenib or vemurafenib plus cobimetinib and therapy outcome.

methodsThis multicenter retrospective study included patients with BRAF V600-mutated irresectable AJCC-v8 stage IIIC/D to IV metastatic melanoma who received treatment with vemurafenib (VEM) or vemurafenib plus cobimetinib (COBIVEM). The development of an early exanthema within six weeks after therapy start and its grading according to CTCAEv4.0 criteria was correlated to therapy outcome in terms of best overall response, progression-free (PFS), and overall survival (OS).

resultsA total of 422 patients from 16 centers were included (VEM, n=299; COBIVEM, n=123). 20.4% of VEM and 43.1% of COBIVEM patients developed an early exanthema. In the VEM cohort, objective responders (CR/PR) more frequently presented with an early exanthema than non-responders (SD/PD); 59.0% versus 38.7%; p=0.0027. However, median PFS and OS did not differ between VEM patients with or without an early exanthema (PFS, 6.9 versus 6.0 months, p=0.65; OS, 11.0 versus 12.4 months, p=0.69). In the COBIVEM cohort, 66.0% of objective responders had an early exanthema compared to 54.3% of non-responders (p=0.031). Median survival times were significantly longer for patients who developed an early exanthema compared to patients who did not (PFS, 9.7 versus 5.6 months, p=0.013; OS, not reached versus 11.6 months, p=0.0061). COBIVEM patients with a mild early exanthema (CTCAEv4.0 grade 1-2) had a superior survival outcome as compared to COBIVEM patients with a severe (CTCAEv4.0 grade 3-4) or non early exanthema, respectively (p=0.047). This might be caused by the fact that 23.6% of patients with severe exanthema underwent a dose reduction or discontinuation of COBIVEM compared to only 8.9% of patients with mild exanthema.

conclusionsThe development of an early exanthema within 6 weeks after treatment start indicates a favorable therapy outcome upon vemurafenib plus cobimetinib. Patients presenting with an early exanthema should therefore be treated with adequate supportive measures to provide that patients can stay on treatment.

Indexed as

BRAF/MEK inhibitioncobimetinibmelanomaskin toxicitytherapy outcomevemurafenib

Identifiers

PMID34109122
PMCPMC8183381
OpenAlexW3163996556

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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.