Evidence map›Paper›PMID 29754934›Full record

Trial reportClinical genitourinary cancer2018

Comprehensive Genomic Profiling of Metastatic Tumors in a Phase 2 Biomarker Study of Everolimus in Advanced Renal Cell Carcinoma.

Xin Gao, Opeyemi Jegede, Connor Gray, Paul J Catalano, Jesse Novak, David J Kwiatkowski, Rana R McKay, Daniel J George, Toni K Choueiri, David F McDermott and 2 more

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

Trial report in Clinical genitourinary cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 27% 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

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Review
  3. Genomic profiling in renal cell carcinoma.Nature reviews. Nephrology · 2020
    Review
  4. Review
  5. Article
  6. Review
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

12 authors at 5 institutions in 1 country.

Xin GaoDivision of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Opeyemi JegedeDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Connor GrayDivision of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Paul J CatalanoDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA.
Jesse NovakDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
David J KwiatkowskiDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Rana R McKayLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Daniel J GeorgeDivision of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University School of Medicine, Durham, NC.
Toni K ChoueiriLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
David F McDermottDivision of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Sabina SignorettiDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Rupal S BhattDivision of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. Electronic address: rbhatt@bidmc.harvard.edu.
Harvard University · USBeth Israel Deaconess Medical Center · USBrigham and Women's Hospital · USDana-Farber Cancer Institute · USDuke Medical Center · US

Funding

Harvard Clinical and Translational Science CenterUL1TR001102 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$106.2M
Treating the P13-Kinase/AKTP50CA101942 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Wanling Xie · 2003 to 2026
$53.4M
Combating Resistance to Antiangiogenic Therapy in Renal Cell CarcinomaR01CA196996 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BHATT, RUPAL S · 2015 to 2019
$2.0M
Mechanism of Acquired Resistance to VEGF-R Antagonists in RCCK08CA138900 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BHATT, RUPAL S · 2010 to 2014
$848k
NCATS NIH HHS UL1 TR001102NCI NIH HHS K08 CA138900NCI NIH HHS P50 CA101942NCI NIH HHS R01 CA196996
6 · The paper itself

Abstract

introductionGenomic events leading to activation of mechanistic target of rapamycin (mTOR) are common in renal cell carcinoma (RCC). Everolimus is an allosteric mTOR inhibitor with efficacy in metastatic RCC. We characterized the genomic profile of RCC tumors from metastatic sites and assessed whether particular alterations correlate with clinical response to everolimus. PATIENTS AND

methodsAn open-label, single-arm phase 2 biomarker study of everolimus 10 mg daily was conducted in metastatic RCC patients. Needle biopsy or metastasectomy was performed on metastatic tumors before everolimus initiation. Next-generation sequencing was performed using a targeted hybrid capture panel detecting alterations within exons and key introns of ≥ 300 cancer-associated genes. Disease assessments were obtained every 8 weeks using standard radiographic modalities and evaluated by Response Evaluation Criteria in Solid Tumors criteria.

resultsObjective response was seen in 1 (4.2%) of 24 patients. Two patients (8.3%) had stable disease lasting > 6 months. Median (90% confidence interval) overall and progression-free survival were 20.1 (8.6, NA) and 3.8 (2.4, 5.4) months, respectively. Next-generation sequencing was successful on 18 pretreatment specimens and 3 on-treatment specimens. Alterations in the phosphatidylinositol 3-kinase-protein kinase B-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway were identified in 8 (44%) of 18 pretreatment samples. An mTOR E2419D mutation was identified in the patient who experienced partial response. Alterations in VHL, PBRM1, SETD2, KDM5C, and ATM were common in the RCC metastases before initiation of everolimus.

conclusionNearly half of heavily pretreated RCC metastases may harbor mutations in components of the PI3K-AKT-mTOR pathway. Commonly mutated genes in primary RCC were also altered at a high frequency in RCC metastases.

Indexed as

AgedAged, 80 and overBiopsy, NeedleCarcinoma, Renal CellEverolimusFemaleHigh-Throughput Nucleotide SequencingHumansKidney NeoplasmsMaleMiddle AgedMutationNeoplasm MetastasisSequence Analysis, DNASignal TransductionEverolimusMetastatic kidney cancermTORNext-generation sequencingTargeted therapy

Identifiers

PMID29754934
PMCPMC6175670
OpenAlexW2802855637

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.