Evidence map›Paper›PMID 37827067›Full record

ArticleEuropean journal of cancer (Oxford, England : 1990)2023

Long-term outcomes and persistent toxicities following BRAF/MEK inhibitor therapy for advanced melanoma.

Rachel S Goodman, Lorenza Di Guardo, Andrea Maurichi, Brendan Kirwin, Adnan Khattak, Vito Vanella, Joanna Lee, Aleigha Lawless, Juliane Czapla, Andrea Spagnoletti and 13 more

Open access · greenAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of cancer (Oxford, England : 1990), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
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  6. 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

23 authors at 10 institutions in 4 countries.

Rachel S GoodmanVanderbilt University School of Medicine, Nashville, TN, USA.
Lorenza Di GuardoDepartment of Medical Oncology, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Milano Province, Italy.
Andrea MaurichiDepartment of Medical Oncology, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Milano Province, Italy.
Brendan KirwinDepartment of Medical Oncology, Melanoma Institute of Australia, The University of Sydney, Mater and Royal North Shore Hospitals, Sydney, NSW, Australia.
Adnan KhattakDepartment of Medical Oncology, Fiona Stanley Hospital, Edith Cowan University, Perth, WA, Australia.
Vito VanellaMelanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione 'G. Pascale', Napoli, Napoli Province, Italy.
Joanna LeeDepartment of Medical Oncology, Blacktown and Westmead Hospitals, Sydney, New South Wales, Australia.
Aleigha LawlessMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Juliane CzaplaMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Andrea SpagnolettiDepartment of Medical Oncology, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Milano Province, Italy.
Margherita AmbrosiniDepartment of Medical Oncology, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Milano Province, Italy.
Elisabeth LivingstoneDepartment of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, North Rhine Westphalia, Germany.
Georgina V LongDepartment of Medical Oncology, Melanoma Institute of Australia, The University of Sydney, Mater and Royal North Shore Hospitals, Sydney, NSW, Australia.
Ryan J SullivanDivision of Hematology and Medical Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Matteo S CarlinoDepartment of Medical Oncology, Blacktown and Westmead Hospitals, Sydney, New South Wales, Australia; Melanoma Institute of Australia, The University of Sydney, Sydney, New South Wales, Australia.
Victoria AtkinsonUniversity of Queensland, Princess Alexandra Hospital, Greenslopes Private Hospital, Brisbane, QLD, Australia.
Claudia TrojanelloMelanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione 'G. Pascale', Napoli, Napoli Province, Italy.
Paolo A AsciertoMelanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione 'G. Pascale', Napoli, Napoli Province, Italy.
Dirk SchadendorfDepartment of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, North Rhine Westphalia, Germany.
Lydia WarburtonDepartment of Medical Oncology, Fiona Stanley Hospital, Edith Cowan University, Perth, WA, Australia.
Alexander M MenziesDepartment of Medical Oncology, Melanoma Institute of Australia, The University of Sydney, Mater and Royal North Shore Hospitals, Sydney, NSW, Australia.
Mario SantinamiDepartment of Medical Oncology, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Milano Province, Italy.
Douglas B JohnsonDivision of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: douglas.b.johnson@vumc.org.
Fondazione IRCCS Istituto Nazionale dei Tumori · ITThe University of Sydney · AUHarvard University · USIstituto Nazionale Tumori IRCCS "Fondazione G. Pascale" · ITEdith Cowan University · AUUniversity of Duisburg-Essen · DEThe University of Queensland · AUVanderbilt University · USVanderbilt University Medical Center · USWestmead Hospital · AU

Funding

Long-Term Cardiovascular Sequelae of Cancer ImmunotherapiesR01HL155990 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI JOHNSON, DOUGLAS B, MOSLEHI, JAVID J · 2021 to 2025
$3.3M
(PQ8) Patient- and tumor-specific biomarkers and mechanisms that predict irAEs resulting from checkpoint inhibitionR01CA227481 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BALKO, JUSTIN M, JOHNSON, DOUGLAS B · 2019 to 2023
$2.6M
Medical Research CouncilMRFNCI NIH HHS R01 CA227481NHLBI NIH HHS R01 HL155990Wellcome Trust
6 · The paper itself

Abstract

backgroundRecent studies have shown that approximately 20% of patients have 4-5 year progression free survival (PFS) on BRAF/MEK inhibitors. The long-term safety and efficacy in these patients with more durable responses have not been studied.

methodsThis retrospective multicenter cohort study assessed response, progression, and adverse events in patients from eight institutions in four countries with >4-year PFS following BRAF/MEK inhibitors.

resultsAmong 146 patients, 112 (76.7%) remained progression-free at median follow-up of 7.8 years from treatment start; 131 (89.7%) were alive. Among progressors (n = 34), 21 (62%) were on treatment at progression. Among those who discontinued treatment for reasons other than progression (toxicity, preference, etc.) (n = 68, with median 49 months treatment duration), 13 (19%) progressed (median 15.3 months from treatment cessation to progression). Surgery or radiation for single-organ progression resulted in durable benefit in 11 of 22 patients (50%). Subsequent systemic therapy included immune therapy (24% responded) and BRAF/MEK rechallenge (56% responded). Thirteen (8.9%) patients had ongoing toxicities at last follow-up, 10 (77%) of which remained on active treatment; all cardiac adverse events had resolved (n = 9). Twenty-four (16.4%) patients developed any new primary cancer, and 28 (19%) patients experienced other major health events.

conclusionsOver 75% of patients with 4-year PFS from BRAF/MEK inhibitors had continued durable antitumor responses after nearly 8-year median follow-up, with similar results in patients who discontinued therapy for reasons other than progression. Long-term toxicities were uncommon and low-grade. These findings highlight the often-favourable outcomes in patients with extended benefit from BRAF/MEK inhibitors.

Indexed as

MelanomaSkin NeoplasmsAntineoplastic Combined Chemotherapy ProtocolsCohort StudiesHumansMitogen-Activated Protein Kinase KinasesMutationProtein Kinase InhibitorsProto-Oncogene Proteins B-rafBRAF protein, humanMitogen-Activated Protein Kinase KinasesProtein Kinase InhibitorsProto-Oncogene Proteins B-rafAdverse eventsBRAF/MEK inhibitorsMelanomaTargeted therapy

Identifiers

PMID37827067
PMCPMC10843257
OpenAlexW4386954547

What OpenQuestion holds

Textmetadata
LicenceTDM
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.