Evidence map›Paper›PMID 28049139›Full record

Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2017

A randomized phase 2 study of MK-2206 versus everolimus in refractory renal cell carcinoma.

E Jonasch, E Hasanov, P G Corn, T Moss, K R Shaw, S Stovall, V Marcott, B Gan, S Bird, X Wang and 6 more

Open access · bronzeAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
4.6field-weighted citation impact, top 5% 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

32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.

  1. Targeted therapy for metastatic renal cell carcinoma.The Cochrane database of systematic reviews · 2020
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 1 country.

E JonaschDivision of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson, Houston, TX, USA.
E HasanovDivision of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson, Houston, TX, USA.
P G CornDivision of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson, Houston, TX, USA.
T MossDivision of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson, Houston, TX, USA.
K R ShawDivision of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson, Houston, TX, USA.
S StovallDivision of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson, Houston, TX, USA.
V MarcottDivision of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson, Houston, TX, USA.
B GanDivision of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson, Houston, TX, USA.
S BirdDivision of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson, Houston, TX, USA.
X WangDivision of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson, Houston, TX, USA.
K A DoDivision of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson, Houston, TX, USA.
P F AltamiranoDivision of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson, Houston, TX, USA.
A J ZuritaDivision of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson, Houston, TX, USA.
L A DoyleInvestigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland, USA.
P N LaraUC Davis Comprehensive Cancer Center, Sacramento, CA, USA.
N M TannirDivision of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson, Houston, TX, USA.
The University of Texas MD Anderson Cancer Center · USNational Cancer Institute · USUniversity of California, Davis · US

Funding

Phase I Molecular and Clinical Pharmacodynamic Trials ETCTNUM1CA186717 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI A. Dimitrios Colevas, Alexey V. Danilov · 2014 to 2026
$19.8M
Mechanistic studies of cancer cell adaptive response to PI3K/AKT inhibitionR01CA190370 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GAN, BOYI · 2015 to 2020
$1.8M
NCI NIH HHS R01 CA190370NCI NIH HHS UM1 CA186717
6 · The paper itself

Abstract

Background: Activation of the phosphoinisitide-3 kinase (PI3K) pathway through mutation and constitutive upregulation has been described in renal cell carcinoma (RCC), making it an attractive target for therapeutic intervention. We performed a randomized phase II study in vascular endothelial growth factor (VEGF) therapy refractory patients to determine whether MK-2206, an allosteric inhibitor of AKT, was more efficacious than the mammalian target of rapamycin inhibitor everolimus. Patients and methods: A total of 43 patients were randomized in a 2:1 distribution, with 29 patients assigned to the MK-2206 arm and 14 to the everolimus arm. Progression-free survival (PFS) was the primary endpoint. Results: The trial was closed at the first futility analysis with an observed PFS of 3.68 months in the MK-2206 arm and 5.98 months in the everolimus arm. Dichotomous response rate profiles were seen in the MK-2206 arm with one complete response and three partial responses in the MK-2206 arm versus none in the everolimus arm. On the other hand, progressive disease was best response in 44.8% of MK2206 versus 14.3% of everolimus-treated patients. MK-2206 induced significantly more rash and pruritis than everolimus, and dose reduction occurred in 37.9% of MK-2206 versus 21.4% of everolimus-treated patients. Genomic analysis revealed that 57.1% of the patients in the PD group had either deleterious TP53 mutations or ATM mutations or deletions. In contrast, none of the patients in the non-PD group had TP53 or ATM defects. No predictive marker for response was observed in this small dataset. Conclusions: Dichotomous outcomes are observed when VEGF therapy refractory patients are treated with MK-2206, and MK-2206 does not demonstrate superiority to everolimus. Additionally, mutations in DNA repair genes are associated with early disease progression, indicating that dysregulation of DNA repair is associated with a more aggressive tumor phenotype in RCC.

Indexed as

AgedAged, 80 and overAntineoplastic AgentsCarcinoma, Renal CellDisease-Free SurvivalEverolimusFemaleHeterocyclic Compounds, 3-RingHumansKidney NeoplasmsMaleMiddle AgedTreatment OutcomeAntineoplastic AgentsEverolimusHeterocyclic Compounds, 3-RingMK 2206everolimusmetastatic diseaseMK-2206PI3K pathwayRCCrenal cell carcinoma

Identifiers

PMID28049139
PMCPMC5834088
OpenAlexW2561417850

What OpenQuestion holds

Textmetadata
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Registered trials

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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.