Evidence map›Paper›PMID 39720993›Full record

Trial reportThe oncologist2025

A phase II trial of larotrectinib in tumors with NTRK fusions or extremes of NTRK mRNA overexpression identified by comprehensive genomic profiling.

Subotheni Thavaneswaran, Hao-Wen Sim, John Grady, David Espinoza, Min Li Huang, Frank Lin, Margaret McGrath, Jayesh Desai, Michail Charakidis, Michael Brown and 3 more

Abstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The oncologist, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

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

13 authors.

Subotheni ThavaneswaranNHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW 2050, Australia.ORCID 0000-0002-8946-6709
Hao-Wen SimNHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW 2050, Australia.ORCID 0000-0002-2530-0523
John GradyGarvan Institute of Medical Research, Sydney, NSW 2010, Australia.
David EspinozaNHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW 2050, Australia.
Min Li HuangSchool of Clinical Medicine, Faculty of Medicine and Health, University of NSW, Sydney, NSW 2010, Australia.
Frank LinNHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW 2050, Australia.
Margaret McGrathPrincess Alexandra Hospital, Brisbane 4102, Australia.
Jayesh DesaiPeter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria 3002, Australia.
Michail CharakidisRoyal Darwin Hospital, Darwin, NT 0810, Australia.
Michael BrownRAH Cancer Clinical Trials Unit, Royal Adelaide Hospital, and Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia.
Maya KansaraThe Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW 2010, Australia.ORCID 0000-0003-1908-3574
John SimesNHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW 2050, Australia.
David ThomasThe Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW 2010, Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTRK-inhibitors have demonstrated efficacy across several cancers with NTRK fusions. Their activity in cancers with NTRK overexpression remains unclear.

methodsThis trial enrolled patients with advanced cancers harboring NTRK fusions or extreme mRNA overexpression, defined as NTRK1/2/3 expression by RNA profiling >5 SDs for a given cancer type. The primary endpoint was objective response rate (ORR), with secondary endpoints including time-to-progression (TTP) ratio [TTP on study to TTP on previous systemic therapy (TTP1)], progression-free survival (PFS), and overall survival (OS). Initially planned for 2 non-comparator groups: primary central nervous system (CNS) and non-CNS tumours with NTRK fusions, the protocol was amended to permit NTRK overexpression.

resultsSeventeen patients were treated with larotrectinib: one glioblastoma with a SPECC1L::NTRK2 fusion (group 1), and a peripheral nerve sheath tumor with a TPM3::NTRK1 fusion and 15 patients with overexpression (group 2). The ORR was 6%. An additional 3 of 12 (25%) TTP1-evaluable patients achieved a TTP ratio ≥1.3 and 2 of 5 without an evaluable TTP1 had a PFS >6 months. Median PFS and OS were 3.5 (95% CI, 1.4-6.0) and 15.9 months (95% CI, 6.4-NR), respectively.

conclusionUnlike its efficacy in NTRK-fusion positive cancers, larotrectinib did not demonstrate a signal of efficacy among tumors with NTRK overexpression.

Indexed as

NeoplasmsOncogene Proteins, FusionPyrazolesPyrimidinesReceptor, trkAReceptor, trkBReceptor, trkCAdultAgedFemaleGene Expression ProfilingHumansMaleMembrane GlycoproteinsMiddle AgedRNA, MessengerlarotrectinibMembrane GlycoproteinsNTRK1 protein, humanNTRK3 protein, humanOncogene Proteins, FusionPyrazolesPyrimidinesReceptor, trkAReceptor, trkBReceptor, trkCRNA, Messengertropomyosin-related kinase-B, humanlarotrectinibNTRK fusionsNTRK overexpressionTRK inhibitor

Identifiers

PMID39720993
PMCPMC12395234

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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.