Evidence map›Paper›PMID 28441383›Full record

ArticleBritish journal of cancer2017

The oral VEGF receptor tyrosine kinase inhibitor pazopanib in combination with the MEK inhibitor trametinib in advanced cholangiocarcinoma.

Rachna T Shroff, Mark Yarchoan, Ashley O'Connor, Denise Gallagher, Marianna L Zahurak, Gary Rosner, Chimela Ohaji, Susan Sartorius-Mergenthaler, Rose Parkinson, Vivek Subbiah and 2 more

Erratum issuedOpen access · hybridAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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
10.9field-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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.

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  8. Combination Therapies for Advanced Biliary Tract Cancer.Journal of clinical and translational hepatology · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Rachna T ShroffThe University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard Unit 426, Houston, TX 77030, USA.
Mark YarchoanGastrointestinal Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans Street, Room 4M10, Baltimore, MD 21287, USA.
Ashley O'ConnorGastrointestinal Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans Street, Room 4M10, Baltimore, MD 21287, USA.
Denise GallagherGastrointestinal Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans Street, Room 4M10, Baltimore, MD 21287, USA.
Marianna L ZahurakGastrointestinal Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans Street, Room 4M10, Baltimore, MD 21287, USA.
Gary RosnerGastrointestinal Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans Street, Room 4M10, Baltimore, MD 21287, USA.
Chimela OhajiThe University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard Unit 426, Houston, TX 77030, USA.
Susan Sartorius-MergenthalerGastrointestinal Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans Street, Room 4M10, Baltimore, MD 21287, USA.
Rose Parkinson
Vivek SubbiahThe University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard Unit 426, Houston, TX 77030, USA.
Ralph ZinnerThe University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard Unit 426, Houston, TX 77030, USA.
Nilofer S AzadGastrointestinal Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans Street, Room 4M10, Baltimore, MD 21287, USA.
Sidney Kimmel Comprehensive Cancer Center · USThe University of Texas MD Anderson Cancer Center · USJohns Hopkins University · US

Funding

ONCOLOGY: CHEMOTHERAPY, IMMUNOLOGY, BIOLOGYT32CA009071 · NCI · JOHNS HOPKINS UNIVERSITY · PI Mary Y Armanios, Nilofer S. Azad · 1985 to 2026
$12.8M
NCI NIH HHS T32 CA009071
6 · The paper itself

Abstract

backgroundCholangiocarcinoma is an aggressive malignancy with limited therapeutic options. MEK inhibition and antiangiogenic therapies have individually shown modest activity in advanced cholangiocarcinoma, whereas dual inhibition of these pathways has not been previously evaluated. We evaluated the safety and efficacy of combination therapy with the oral VEGF receptor tyrosine kinase inhibitor pazopanib plus the MEK inhibitor trametinib in patients with advanced cholangiocarcinoma.

methodsIn this open-label, multicentre, single-arm trial, adults with advanced unresectable cholangiocarcinoma received pazopanib 800 mg daily and trametinib 2 mg daily until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) with secondary end points including overall survival (OS), response rate, and disease control rate (DCR).

resultsA total of 25 patients were enrolled and had received a median of 2 prior systemic therapies (range 1-7). Median PFS was 3.6 months (95% CI: 2.7-5.1) and the 4-month PFS was 40% (95% CI: 24.7-64.6%). There was a trend towards increased 4-month PFS as compared with the prespecified null hypothesised 4-month PFS of 25%, but this difference did not reach statistical significance (P=0.063). The median survival was 6.4 months (95% CI: 4.3-10.2). The objective response rate was 5% (95% CI: 0.13-24.9%) and the DCR was 75% (95% CI: 51%, 91%). Grade 3/4 adverse events attributable to study drugs were observed in 14 (56%) and included thrombocytopenia, abnormal liver enzymes, rash, and hypertension.

conclusionsAlthough the combination of pazopanib plus trametinib had acceptable toxicity with evidence of clinical activity, it did not achieve a statistically significant improvement in 4-month PFS over the prespecified null hypothesised 4-month PFS.

Indexed as

Administration, OralAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBile Duct NeoplasmsCholangiocarcinomaDisease-Free SurvivalDisease ProgressionDrug EruptionsExanthemaFemaleHumansHypertensionIndazolesMaleIndazolesMAP Kinase Kinase KinasespazopanibProtein Kinase InhibitorsPyridonesPyrimidinesPyrimidinonesReceptors, Vascular Endothelial Growth FactorSulfonamidestrametinib

Identifiers

PMID28441383
PMCPMC5520097
OpenAlexW2608084876

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.