Evidence map›Paper›PMID 42168180›Full record

Trial reportNature communications2026

Use of circulating tumour DNA to prospectively guide a switch from targeted to immune therapy in BRAF mutant advanced melanoma: the randomised phase II CAcTUS trial.

Rebecca J Lee, Dominic G Rothwell, Nigel Smith, Shien Chow, Juan Delgado-SanMartin, Hitesh Mistry, Yvonne Sylvestre, Shih-Chieh Chiang, Harry Clarke, Gabriela Gremel and 14 more

Registry-linked trialAbstract readClinical Trial, Phase IIRandomized Controlled TrialMulticenter Study
In one paragraph

Trial report in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03808441 (A Parallel Arm, Biomarker Driven, Phase II Trial to Determine the Role of Circulating Tumour DNA in Guiding a Switch Between Targeted Therapy and Immune Therapy in Patients With Advanced Cutaneous Melanoma), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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.

NCT03808441 phase2unknown statusnot on this map

A Parallel Arm, Biomarker Driven, Phase II Trial to Determine the Role of Circulating Tumour DNA in Guiding a Switch Between Targeted Therapy and Immune Therapy in Patients With Advanced Cutaneous Melanoma

TypeinterventionalSponsorThe Christie NHS Foundation TrustRan2019 to 2024Enrolled21ConditionsMelanomaArmsctDNA analysis
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

24 authors.

Rebecca J Lee *Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. Rebecca.lee-3@manchester.ac.uk.ORCID http://orcid.org/0000-0003-2540-2009
Dominic G Rothwell *Cancer Research UK National Biomarker Centre, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-8757-3893
Nigel SmithCancer Research UK National Biomarker Centre, University of Manchester, Manchester, UK.
Shien ChowDepartment of Medical Oncology, Clatterbridge Cancer Centre, Liverpool, UK.
Juan Delgado-SanMartinNHLI Data Science, Imperial College London, London, UK.ORCID http://orcid.org/0000-0001-7247-0667
Hitesh MistryDivision of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Yvonne SylvestreDivision of Population Health, Health Services Research & Primary Care, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-3288-9006
Shih-Chieh ChiangCancer Inflammation and Immunity Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UK.
Harry ClarkeCancer Research UK National Biomarker Centre, University of Manchester, Manchester, UK.
Gabriela GremelMolecular Oncology Group, Cancer Research UK Manchester Institute, Manchester, UK.
Avinash GuptaThe Christie NHS Foundation Trust, Manchester, UK.
Kimberley HockenhullCancer Inflammation and Immunity Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UK.
Noel KelsoCancer Research UK National Biomarker Centre, University of Manchester, Manchester, UK.
Rohit KochharThe Christie NHS Foundation Trust, Manchester, UK.
Damian MullanThe Christie NHS Foundation Trust, Manchester, UK.
Ruth PlummerSir Bobby Robson Cancer Trials Research Centre, Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0003-0107-1444
Patricio SerraThe Christie NHS Foundation Trust, Manchester, UK.
Heather ShawDepartment of Oncology, University College London Hospitals NHS Foundation Trust, London, UK.
Holly SummersgillDivision of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Samra TurajlicSkin and Renal Units, The Royal Marsden NHS Foundation Trust, London, UK.ORCID http://orcid.org/0000-0001-8846-136X
Florent MouliereCancer Research UK National Biomarker Centre, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0001-7043-0514
Richard MaraisMolecular Oncology Group, Cancer Research UK Manchester Institute, Manchester, UK.ORCID http://orcid.org/0000-0001-7484-4183
Caroline DiveCancer Research UK National Biomarker Centre, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-1726-8850
Paul LoriganDivision of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. paul.lorigan@nhs.net.

Funding

Cancer Research UK (CRUK) CTRNBC-2022/100001, CTRQQR-2021\100010DH | National Institute for Health Research (NIHR) NIHR203308Wellcome TrustWellcome Trust (Wellcome) 225724/Z/22/Z
6 · The paper itself

Abstract

Checkpoint inhibitor immunotherapy (CPI) for BRAF mutant advanced melanoma first-line results in a better long-term survival compared to targeted therapy (TT), however TT induction may benefit poor prognosis groups. The parallel-arm, randomised phase II, multicentre, feasibility CAcTUS trial (Clinicaltrials.gov NCT03808441) randomised 21 patients to receive standard of care investigators choice TT or CPI, switching to the alternative upon progression (n = 10), or commencing TT and switching to CPI upon an ≥80% reduction of BRAF variant allele frequency (VAF) in circulating tumour DNA (ctDNA; n = 11). The study achieved its primary endpoints with 100% (95% confidence interval [CI]: 94-100%) of critical results provided within 7 days to inform a decision to switch and 100% of patients commencing TT achieving an ≥80% reduction of BRAF VAF (95% CI: 80-100%). Secondary outcomes included progression-free survival and overall survival. No new safety signals were observed for TT/CPI. Post-hoc analysis of clinical features, circulating cytokines and chemokines at ctDNA nadir following TT induction suggested a more favourable profile prior to CPI initiation. Longitudinal ctDNA dynamics revealed ctDNA provided an early signal of CPI benefit and that rechallenge with TT following CPI progression resulted in a further ctDNA response. These data support the utility of ctDNA to guide treatment decision-making within a clinically relevant timeframe to optimise treatment scheduling strategies.

Indexed as

Circulating Tumor DNAImmune Checkpoint InhibitorsImmunotherapyMelanomaProto-Oncogene Proteins B-rafFemaleHumansMaleMiddle AgedMolecular Targeted TherapyMutationProgression-Free SurvivalProspective StudiesBRAF protein, humanCirculating Tumor DNAImmune Checkpoint InhibitorsProto-Oncogene Proteins B-raf

Identifiers

PMID42168180
PMCPMC13389006

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Registered trials

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.