Evidence mapPaperPMID 24912489Full record

Trial reportOncotarget2014

Anastrozole and everolimus in advanced gynecologic and breast malignancies: activity and molecular alterations in the PI3K/AKT/mTOR pathway.

Jennifer J Wheler, Stacy L Moulder, Aung Naing, Filip Janku, Sarina A Piha-Paul, Gerald S Falchook, Ralph Zinner, Apostolia M Tsimberidou, Siqing Fu, David S Hong and 4 more

Registry-linked trialOpen access · diamondAbstract readClinical Trial
In one paragraph

Trial report in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01197170 (Hormone Receptor Positive Disease Across Solid Tumor Types), which is not on this map. Cited by 27 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 2 pooled it
3.4field-weighted citation impact, top 7% 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.

NCT01197170 phase1completednot on this map

Hormone Receptor Positive Disease Across Solid Tumor Types: A Phase I Study of Single-Agent Hormone Blockade and Combination Approaches With Targeted Agents to Provide Synergy and Overcome Resistance

TypeinterventionalSponsorM.D. Anderson Cancer CenterRan2010 to 2021Enrolled277ConditionsSolid Tumors, Advanced CancerArmsAnastrozole, Bevacizumab, Everolimus, Sorafenib, Erlotinib
3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 47 citations in OpenAlex.

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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

14 authors at 3 institutions in 1 country.

Jennifer J WhelerDepartment of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
Stacy L MoulderDepartment of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Aung Naing
Filip Janku
Sarina A Piha-Paul
Gerald S Falchook
Ralph Zinner
Apostolia M Tsimberidou
Siqing Fu
David S Hong
Johnique T Atkins
Roman YelenskyFoundation Medicine, Cambridge, MA.
Philip J Stephens
Razelle KurzrockCenter for Personalized Cancer Therapy, Moores Cancer Center, University of California, San Diego, La Jolla, CA.
The University of Texas MD Anderson Cancer Center · USFoundation Medicine (United States)University of California, San Diego · US

Funding

NCATS NIH HHS UL1 TR000371
6 · The paper itself

Abstract

backgroundSince PI3K/AKT/mTOR pathway activation diminishes the effects of hormone therapy, combining aromatase inhibitors (anatrozole) with mTOR inhibitors (everolimus) was investigated. PATIENTS AND

methodsWe evaluated anastrozole and everolimus in 55 patients with metastatic estrogen (ER) and/or progesterone receptor (PR)-positive breast and gynecologic tumors. Endpoints were safety, antitumor activity and molecular correlates.

resultsFull doses of anastrozole (1 mg PO daily) and everolimus (10 mg PO daily) were well tolerated. Twelve of 50 evaluable patients (24%) (median = 3 prior therapies) achieved stable disease (SD) ≥ 6 months/partial response (PR)/complete response (CR) (n = 5 (10%) with PR/CR): 9 of 32 (28%) with breast cancer (n=5 (16%) with PR/CR); 2 of 10 (20%), ovarian cancer; and 1 of 6 (17%), endometrial cancer. Six of 22 patients (27%) with molecular alterations in the PI3K/AKT/mTOR pathway achieved SD ≥ 6 months/PR/CR. Six of 8 patients (75%) with SD ≥ 6 months/PR/CR with molecular testing demonstrated at least one alteration in the PI3K/AKT/mTOR pathway: mutations in PIK3CA (n=3) and AKT1 (n=1) or PTEN loss (n=3). All three responders (CR (n = 1); PR (n=2)) who had next generation sequencing demonstrated additional alterations: amplifications in CCNE1, IRS2, MCL1, CCND1, FGFR1 and MYC and a rearrangement in PRKDC.

conclusionsCombination anastrozole and everolimus is well tolerated at full approved doses, and is active in heavily-pretreated patients with ER and/or PR-positive breast, ovarian and endometrial cancers. Responses were observed in patients with multiple molecular aberrations. CLINICAL TRAILS INCLUDED: NCT01197170.

Indexed as

AdultAgedAged, 80 and overAnastrozoleAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsEverolimusFemaleGenital Neoplasms, FemaleHumansKaplan-Meier EstimateMiddle AgedNitrilesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionAnastrozoleEverolimusMTOR protein, humanNitrilesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSirolimusTOR Serine-Threonine KinasesTriazoles

Identifiers

PMID24912489
PMCPMC4102789
OpenAlexW1540508303

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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 Socratic graph.