Evidence map›Paper›PMID 41537702›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2026

Exploratory Analysis of Biomarkers and Treatment Outcomes from the COLUMBUS Study in BRAF V600E/K-Mutant Advanced or Metastatic Melanoma.

Reinhard Dummer, Shibing Deng, Tao Xie, Nuzhat Pathan, Hedieh Saffari, Caroline Robert, Ana Arance, Jan Willem B de Groot, Claus Garbe, Helen J Gogas and 13 more

Abstract readRandomized Controlled TrialClinical Trial, Phase III
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–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

3 citing papers in PubMed.

  1. Circulating Tumor DNA as a Biomarker for Melanoma Prognosis and Therapy.American journal of clinical dermatology · 2026
    Review
  2. Article
  3. 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

23 authors.

Reinhard DummerUniversity Hospital Zurich , Zurich, Switzerland.ORCID 0000-0002-2279-6906
Shibing DengPfizer , La Jolla, California.ORCID 0000-0002-2867-263X
Tao XiePfizer , La Jolla, California.ORCID 0000-0001-7658-6587
Nuzhat PathanPfizer , La Jolla, California.ORCID 0009-0003-2116-2586
Hedieh SaffariPfizer , South San Francisco, California.ORCID 0009-0007-2680-9122
Caroline RobertGustave Roussy and Paris-Saclay University, Villejuif, France.ORCID 0000-0002-9493-0238
Ana AranceHospital Clinic of Barcelona and IDIBAPS, Barcelona, Spain.ORCID 0000-0003-2896-1957
Jan Willem B de GrootIsala Oncology Center, Zwolle, Netherlands.ORCID 0000-0002-1043-5011
Claus GarbeUniversity Hospital Tübingen , Tübingen, Germany.ORCID 0000-0001-8530-780X
Helen J GogasNational and Kapodistrian University of Athens , Athens, Greece.ORCID 0000-0002-0451-2885
Ralf GutzmerDepartment of Dermatology, Ruhr University Bochum, Minden, Germany.ORCID 0000-0001-7921-2820
Ivana KrajsováGeneral Teaching Hospital in Prague , Prague, Czech Republic.ORCID 0000-0002-1599-6424
Gabriella LiszkayNational Institute of Oncology , Budapest, Hungary.ORCID 0000-0001-6161-2033
Carmen LoquaiDepartment of Dermatology, Fachklinik Hornheide, Muenster, Germany.ORCID 0009-0007-0238-3446
Mario MandalaUniversity of Perugia , Perugia, Italy.ORCID 0000-0001-8846-8959
Dirk SchadendorfUniversity Hospital Essen, West German Cancer Center and German Cancer Consortium, Partner Site Essen, Essen, Germany.ORCID 0000-0003-3524-7858
Naoya YamazakiNational Cancer Center Hospital, Tokyo, Japan.ORCID 0000-0002-9638-0428
Paolo A AsciertoMelanoma Unit, Cancer Immunotherapy and Innovative Therapies, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy.ORCID 0000-0002-8322-475X
Craig B DavisPfizer , La Jolla, California.ORCID 0000-0002-1703-451X
Khyati ShahPfizer , La Jolla, California.ORCID 0000-0002-2510-803X
Phineas HamiltonPfizer , La Jolla, California.ORCID 0000-0001-6993-8505
Alessandra di PietroPfizer , Milan, Italy.ORCID 0009-0009-1887-6610
Keith FlahertyMassachusetts General Hospital Cancer Center, Boston, Massachusetts.ORCID 0000-0002-3402-0478

Funding

Pfizer (Davis)
6 · The paper itself

Abstract

purposeTreatment with encorafenib ± binimetinib is associated with improved survival versus vemurafenib in patients with BRAF V600E/K-mutant advanced melanoma. We retrospectively analyzed genomic and transcriptomic data from the phase III COLUMBUS trial to identify molecular correlates of benefit with encorafenib ± binimetinib. EXPERIMENTAL

designIn COLUMBUS, patients with BRAF V600E/K-mutant locally advanced, unresectable, or metastatic melanoma (n = 921) were randomized to receive encorafenib plus binimetinib, encorafenib, or vemurafenib. We used whole-exome sequencing (n = 666), whole-transcriptome sequencing (RNA sequencing; n = 514), and assessment of circulating tumor DNA (ctDNA) at baseline (n = 336) and on treatment (cycle 2 day 1, n = 184) to evaluate biomarker associations with progression-free and overall survival.

resultsSurvival benefits with encorafenib plus binimetinib versus vemurafenib were greatest in patients with higher tumor mutational burden (TMB) and those with evidence of tumor immune infiltration (i.e., higher cytolytic score, PD-L1 expression, or IFNγ gene signature scores). Clustering of gene expression profiles identified three tumor subgroups, including an "immune" subgroup associated with improved survival. Detection of BRAF V600 alterations in baseline ctDNA was associated with shorter survival; clearance of BRAF V600 alterations at cycle 2 day 1 was associated with improved survival across arms.

conclusionsThe greatest benefits of encorafenib plus binimetinib were observed in patients with evidence of high TMB and/or tumor-immune infiltration, suggesting potential immune contributions to efficacy, which were not observed with vemurafenib. BRAF V600 detectability in ctDNA seems to have utility as a marker of prognosis and response in this population.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorMelanomaMutationProto-Oncogene Proteins B-rafAdultAgedBenzimidazolesCarbamatesExome SequencingFemaleHumansMaleMiddle AgedNeoplasm MetastasisRetrospective StudiesBenzimidazolesbinimetinibBiomarkers, TumorBRAF protein, humanCarbamatesencorafenibProto-Oncogene Proteins B-rafSulfonamidesVemurafenib

Identifiers

PMID41537702
PMCPMC13040209

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.