Evidence map›Paper›PMID 41606118›Full record

Trial reportNature medicine2026

Neoadjuvant ipilimumab plus nivolumab in melanoma: 5-year survival and biomarker analysis from the phase 2 PRADO-trial.

Lotte L Hoeijmakers, Petros Dimitriadis, Steven C M A Wijnen, Irene L M Reijers, Marta Lopez-Yurda, Alexander M Menzies, Annegien Broeks, Sten Cornelissen, Alejandro Torres Acosta, Anja van der Wal and 33 more

Registry-linked trialAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Publisher
In one paragraph

Trial report in Nature medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02977052 (Multicenter Phase 2 Study to Identify of the Optimal Neo-Adjuvant Combination Scheme of Ipilimumab and Nivolumab), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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.

NCT02977052 phase2unknown statusnot on this map

Multicenter Phase 2 Study to Identify of the Optimal Neo-Adjuvant Combination Scheme of Ipilimumab and Nivolumab (OpACIN-neo)

TypeinterventionalSponsorThe Netherlands Cancer InstituteRan2016 to 2025Enrolled186ConditionsMalignant Melanoma Stage IIIArmsIpilimumab, Nivolumab, Surgery, Blood for PBMCs, Biopsies
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
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

43 authors.

Lotte L HoeijmakersDepartment of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0009-0003-8431-7557
Petros Dimitriadis *Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-3546-285X
Steven C M A Wijnen *Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0009-0009-9985-0753
Irene L M ReijersDepartment of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Marta Lopez-YurdaDepartment of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0003-3678-3222
Alexander M MenziesMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Annegien BroeksCore Facility Molecular Pathology & Biobanking Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, The Netherlands.
Sten CornelissenCore Facility Molecular Pathology & Biobanking Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, The Netherlands.
Alejandro Torres AcostaDepartment of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Anja van der WalDepartment of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Robyn P M SawMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-3354-806X
Judith M VersluisDepartment of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-3423-9912
Winan J van HoudtDepartment of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Michel W WoutersDepartment of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-6173-0662
Jurriaan RomanoDepartment of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0009-0004-5201-1411
Eliza A RozemanDepartment of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Lindsay G Grijpink-OngeringDepartment of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Ellen KapiteijnDepartment of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.ORCID http://orcid.org/0000-0002-4814-6426
Astrid A M van der VeldtDepartments of Medical Oncology and Radiology & Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Karijn P M SuijkerbuijkDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0003-3604-5430
Hanna ErikssonDepartment of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
Geke A P HospersDepartment of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID http://orcid.org/0000-0002-3047-7892
Jos A van der HageDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.ORCID http://orcid.org/0000-0001-9040-1323
Dirk J GrünhagenDepartment of Surgical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0001-8293-6002
Arjen J WitkampDepartment of Surgical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Judith M LijnsveltDepartment of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Willem M C KlopDepartment of Head and Neck Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Charlotte L ZuurDepartment of Head and Neck Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-1777-012X
Annemarie BruiningDepartment of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Abrahim Al-MamganiDepartment of Radiotherapy, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Thomas E PenningtonMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Kerwin F ShannonMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0001-8538-3132
Sydney Ch'ngMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-4011-1253
Andrew J ColebatchMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Maria GonzalezMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-2197-6657
Andrew J SpillaneMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-9520-0181
John B A G HaanenDepartment of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-5884-7704
Robert V RawsonMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Richard A ScolyerMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-8991-0013
Bart A van de WielDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Alexander C J van AkkooiMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-3262-6935
Georgina V LongMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0001-8894-3545
Christian U BlankDepartment of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. c.blank@nki.nl.ORCID http://orcid.org/0000-0002-7945-5846

Funding

Bristol-Myers Squibb (Bristol-Myers Squibb Company) CA209-701Department of Health | National Health and Medical Research Council (NHMRC) 2022/GNT2018514
6 · The paper itself

Abstract

Neoadjuvant ipilimumab plus nivolumab has become standard therapy for stage III melanoma based on the NADINA trial, although long-term data are lacking. In the phase 2 PRADO cohort of OpACIN-neo, 99 patients with stage III macroscopic melanoma received this regimen. Here we report first-time 5-year survival data: 71% event-free survival, 74% relapse-free survival, 79% distant metastasis-free survival and 86% overall survival. Ongoing grade 1-2 immune-related adverse events occurred in 69% of patients alive, predominantly vitiligo and hypothyroidism. Major pathologic response (MPR), high tumor mutational burden (TMB), high interferon-gamma (IFNγ) signature and programmed cell death ligand 1 (PD-L1) expression of 1% or higher were associated with favorable outcomes. Combined high TMB, IFNγ and PD-L1 expression yielded 100% MPR and 100% 5-year event-free survival, whereas triple low expression had only 18% MPR and 41% event-free survival. Our findings demonstrate favorable long-term outcomes for patients with an MPR and identify IFNγ and PD-L1 as promising baseline biomarkers. ClinicalTrials.gov identifier: NCT02977052 .

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorIpilimumabMelanomaNivolumabSkin NeoplasmsAdultAgedB7-H1 AntigenDisease-Free SurvivalFemaleHumansInterferon-gammaMaleMiddle AgedNeoadjuvant TherapyB7-H1 AntigenBiomarkers, TumorCD274 protein, humanInterferon-gammaIpilimumabNivolumab

Identifiers

PMID41606118

What OpenQuestion holds

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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.