Evidence map›Paper›PMID 20857170›Full record

Trial reportInvestigational new drugs2012

Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors.

Matthew D Galsky, Daniel D Von Hoff, Marcus Neubauer, Thomas Anderson, Mark Fleming, Yasir Nagarwala, Janine M Mahoney, Dawn Midwinter, Linda Vocila, Tal Z Zaks

Abstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Investigational new drugs, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 9% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.

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  18. Dual HER2 targeting impedes growth of HER2 gene-amplified uterine serous carcinoma xenografts.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014
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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

10 authors at 6 institutions in 4 countries.

Matthew D GalskyMount Sinai Medical Center/Tisch Cancer Institute, 1 Gustave L Levy Place, New York, NY 10029, USA. Matthew.galsky@mssm.edu
Daniel D Von Hoff
Marcus Neubauer
Thomas Anderson
Mark Fleming
Yasir Nagarwala
Janine M Mahoney
Dawn Midwinter
Linda Vocila
Tal Z Zaks
The US Oncology Network · USGlaxoSmithKline (Netherlands) · NLTranslational Genomics Research Institute · USGlaxoSmithKline (United Kingdom) · GBGlaxoSmithKline (United States) · USMount Sinai Hospital · US

Funding

NCI NIH HHS #5PO1CA109522
6 · The paper itself

Abstract

backgroundTo explore the activity of lapatinib with a novel trial design focused on the drug target rather than on histology.

methodsPatients with HER2 amplified gastro-esophageal, bladder, ovarian, or uterine tumors were enrolled into a double-blinded randomized discontinuation study of lapatinib 1,500 mg PO daily. The planned sample size was 250 patients with HER2 amplified tumors, with the goal of randomizing 100 patients with stable disease (SD) at week 12 to either lapatinib or placebo. Patients responding after 12 weeks continued on lapatinib; those who progressed were discontinued from study. The primary objectives were response rate after 12 weeks and the percentage of patients who remained progression free 12 weeks after randomization to placebo versus lapatinib. Secondary objectives were duration of response and determination of the incidence of HER2 amplification in multiple tumor types.

resultsA total of 141 patients were screened and 32 patients with HER2 amplified tumors were enrolled. At week 12, 1 (3%) patient had a complete response, 9 (28%) had stable disease, 20 (63%) had progressive disease, and 2 (6%) were unknown. Only 7 patients with SD underwent randomization. The low response rate coupled with slow screening and enrollment led to early study closure.

conclusionsBasing trial eligibility on the presence of a genetic target, versus histologic classification, is challenging. While HER2 amplifications appear to be prevalent in select non-breast tumors, lapatinib monotherapy is associated with modest activity. The target-specific histology-independent randomized discontinuation design still merits consideration for targets clearly implicated in "oncogene addiction".

Indexed as

Gene AmplificationMolecular Targeted TherapyAdultAgedAged, 80 and overAntineoplastic AgentsBiomarkers, TumorDisease-Free SurvivalDouble-Blind MethodDrug Administration ScheduleErb-b2 Receptor Tyrosine KinasesFemaleHumansIn Situ Hybridization, FluorescenceLapatinibMaleAntineoplastic AgentsBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesLapatinibProtein Kinase InhibitorsQuinazolines

Identifiers

PMID20857170
OpenAlexW1974989473

What OpenQuestion holds

Textmetadata
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.