Evidence map›Paper›PMID 32105622›Full record

Trial reportThe Lancet. Oncology2020

Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials.

David S Hong, Steven G DuBois, Shivaani Kummar, Anna F Farago, Catherine M Albert, Kristoffer S Rohrberg, Cornelis M van Tilburg, Ramamoorthy Nagasubramanian, Jordan D Berlin, Noah Federman and 19 more

Open access · greenAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 562 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
562citing papers in PubMed, 8 pooled it
78.2field-weighted citation impact, top 1% 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

562 citing papers in PubMed, 8 syntheses or guidelines pooled it, 963 citations in OpenAlex.

  1. SEOM-GEICAM-SOLTI clinical guidelines in advanced breast cancer (UPDATE 2025).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Guideline
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  7. Pooled it
  8. Pooled it
  9. Trial
  10. Trial
  11. Review
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  15. Article
  16. Updated Asian consensus guidelines for the diagnosis and management of gastrointestinal stromal tumor (2025).Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026
    Review
  17. Therapeutic vaccines for NSCLC: From mechanisms to clinical translation.Chinese medical journal pulmonary and critical care medicine · 2026
    Review
  18. Article
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  20. Article

502 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 20 institutions in 6 countries.

David S HongUniversity of Texas MD Anderson Cancer Center, Houston, TX, USA.
Steven G DuBoisDana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA, USA.
Shivaani KummarStanford University School of Medicine, Stanford University, Palo Alto, CA, USA.
Anna F FaragoMassachusetts General Hospital, Boston, MA, USA.
Catherine M AlbertSeattle Children's Hospital, University of Washington, Seattle, WA, USA.
Kristoffer S RohrbergRigshospitalet, Copenhagen University, Copenhagen, Denmark.
Cornelis M van TilburgHopp Children's Cancer Center Heidelberg, Heidelberg University Hospital, Heidelberg, Germany; German Cancer Research Center, Heidelberg, Germany.
Ramamoorthy NagasubramanianNemours Children's Hospital, Orlando, FL, USA.
Jordan D BerlinVanderbilt University Medical Center, Nashville, TN, USA.
Noah FedermanDavid Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Leo MascarenhasSaban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Birgit GeoergerGustave Roussy Cancer Center, Department of Pediatric and Adolescent Oncology, Université Paris-Saclay, Villejuif, France.
Afshin DowlatiUniversity Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Alberto S PappoSt Jude Children's Research Hospital, Memphis, TN, USA.
Stefan BielackKlinikum Stuttgart-Olgahospital, Stuttgart Cancer Center, Pediatrics 5 (Oncology, Hematology, Immunology), Stuttgart, Germany.
François DozSIREDO Center Care, Innovation, Research In Pediatric, Adolescent and Young Adult Oncology, Institut Curie and Paris Descartes University, Paris, France.
Ray McDermottSt Vincent's University Hospital and Cancer Trials Ireland, Dublin, Ireland.
Jyoti D PatelUniversity of Chicago, Chicago, IL, USA.
Russell J SchilderSidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Makoto TaharaNational Cancer Center Hospital East, Kashiwa, Japan.
Stefan M PfisterHopp Children's Cancer Center Heidelberg, Heidelberg University Hospital, Heidelberg, Germany; German Cancer Research Center, Heidelberg, Germany; German Cancer Network, Heidelberg, Germany.
Olaf WittHopp Children's Cancer Center Heidelberg, Heidelberg University Hospital, Heidelberg, Germany; German Cancer Research Center, Heidelberg, Germany.
Marc LadanyiMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Erin R RudzinskiSeattle Children's Hospital, Seattle, WA, USA.
Shivani NandaBayer HealthCare Pharmaceuticals, Whippany, NJ, USA.
Barrett H ChildsBayer HealthCare Pharmaceuticals, Whippany, NJ, USA.
Theodore W LaetschUniversity of Texas Southwestern Medical Center/Children's Health, Dallas, TX, USA.
David M HymanMemorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
Alexander DrilonMemorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA. Electronic address: drilona@mskcc.org.
Bayer (United States) · USCornell University · USSeattle Children's Hospital · USCopenhagen University Hospital · DKDana-Farber/Boston Children's Cancer and Blood Disorders Center · USGerman Cancer Research Center · DEHopp Children's Cancer Center Heidelberg · DEInstitut Gustave Roussy · FRKlinikum Stuttgart · DEMassachusetts General Hospital · USMemorial Sloan Kettering Cancer Center · USNational Cancer Center Hospital East · JPNemours Children's Clinic · USStanford University · USSt. Jude Children's Research Hospital · USSt. Vincent's University Hospital · IEThe University of Texas MD Anderson Cancer Center · USThe University of Texas Southwestern Medical Center · USThomas Jefferson University · USUniversité Paris Cité · FR

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4M
Understanding tumor addiction to TRK fusions and sensitivity to TRK inhibitionR01CA226864 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI DRILON, ALEXANDER, VENTURA, ANDREA · 2018 to 2021
$2.5M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA014089NCI NIH HHS R01 CA226864
6 · The paper itself

Abstract

backgroundThe selective TRK inhibitor larotrectinib was approved for paediatric and adult patients with advanced TRK fusion-positive solid tumours based on a primary analysis set of 55 patients. The aim of our analysis was to explore the efficacy and long-term safety of larotrectinib in a larger population of patients with TRK fusion-positive solid tumours.

methodsPatients were enrolled and treated in a phase 1 adult, a phase 1/2 paediatric, or a phase 2 adolescent and adult trial. Some eligibility criteria differed between these studies. For this pooled analysis, eligible patients were aged 1 month or older, with a locally advanced or metastatic non-CNS primary, TRK fusion-positive solid tumour, who had received standard therapy previously if available. This analysis set includes the 55 patients on which approval of larotrectinib was based. Larotrectinib was administered orally (capsule or liquid formulation), on a continuous 28-day schedule, to adults mostly at a dose of 100 mg twice daily, and to paediatric patients mostly at a dose of 100 mg/m

findingsBetween May 1, 2014, and Feb 19, 2019, 159 patients with TRK fusion-positive cancer were enrolled and treated with larotrectinib. Ages ranged from less than 1 month to 84 years. The proportion of patients with an objective response according to investigator assessment was 121 (79%, 95% CI 72-85) of 153 evaluable patients, with 24 (16%) having complete responses. In a safety population of 260 patients treated regardless of TRK fusion status, the most common grade 3 or 4 larotrectinib-related adverse events were increased alanine aminotransferase (eight [3%] of 260 patients), anaemia (six, 2%), and decreased neutrophil count (five [2%]). The most common larotrectinib-related serious adverse events were increased alanine aminotransferase (two [<1%] of 260 patients), increased aspartate aminotransferase (two [<1%]), and nausea (two [<1%]). No treatment-related deaths occurred.

interpretationThese data confirm that TRK fusions define a unique molecular subgroup of advanced solid tumours for which larotrectinib is highly active. Safety data indicate that long-term administration of larotrectinib is feasible.

fundingBayer and Loxo Oncology.

Indexed as

AdolescentAdultAgedAged, 80 and overChildChild, PreschoolFemaleHumansInfantInfant, NewbornMaleMiddle AgedNeoplasmsProteinsPyrazolesPyrimidineslarotrectinibProteinsPyrazolesPyrimidinesTFG protein, humanVesicular Transport Proteins

Identifiers

PMID32105622
PMCPMC7497841
OpenAlexW3008107700

What OpenQuestion holds

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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.