Evidence map›Paper›PMID 23743569›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2013

Phase II study of everolimus in patients with metastatic colorectal adenocarcinoma previously treated with bevacizumab-, fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens.

Kimmie Ng, Josep Tabernero, Jimmy Hwang, Emilio Bajetta, Sunil Sharma, Salvatore A Del Prete, Edward R Arrowsmith, David P Ryan, Michaela Sedova, Jin Jin and 2 more

Open access · bronzeAbstract readClinical Trial, Phase IIMulticenter Study
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 8% 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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.

  1. Treatment-related fatigue with everolimus and temsirolimus in patients with cancer-a meta-analysis of clinical trials.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015
    Pooled it
  2. Trial
  3. Trial
  4. Review
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  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
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  12. Review
  13. PI3K/Akt/mTOR Signaling Pathway as a Target for Colorectal Cancer Treatment.International journal of molecular sciences · 2024
    Review
  14. Article
  15. Metformin inhibits the development and metastasis of colorectal cancer.Medical oncology (Northwood, London, England) · 2022
    Article
  16. Article
  17. Article
  18. eLife · 2021
    Article
  19. Article
  20. 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 3 institutions in 2 countries.

Kimmie NgDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana 1220, Boston, MA 02215, USA. Kimmie_Ng@dfci.harvard.edu
Josep Tabernero
Jimmy Hwang
Emilio Bajetta
Sunil Sharma
Salvatore A Del Prete
Edward R Arrowsmith
David P Ryan
Michaela Sedova
Jin Jin
Kamel Malek
Charles S Fuchs
Dana-Farber Cancer Institute · USGeorgetown University · USNovartis (Switzerland) · CH

Funding

Role of Vitamin D, Inflammation, and Energy Balance in Colorectal Cancer SurvivalK07CA148894 · NCI · DANA-FARBER CANCER INST · PI NG, KIMMIE · 2011 to 2015
$889k
NCI NIH HHS K07 CA148894
6 · The paper itself

Abstract

purposeDysregulation of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway is seen in 40% to 60% of patients with colorectal cancer. Everolimus, an oral inhibitor of mTOR, showed efficacy in patients with metastatic colorectal cancers in phase I studies. EXPERIMENTAL

designIn sequential phase II studies assessing two dosing schedules, patients with metastatic colorectal cancers refractory to bevacizumab-, fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens received everolimus 70 mg/wk (n = 99) or 10 mg/d (n = 100). Primary endpoints were disease control rate (DCR) and objective response rate; secondary endpoints included progression-free survival (PFS), overall survival (OS), and duration of response or stable disease (SD). Tumor tissue was collected from all patients for predefined exploratory biomarker analyses.

resultsSeventy-one patients were included in the per-protocol set for each cohort. DCRs of 31.0% and 32.4% (all SD) were seen in the weekly and daily schedules, respectively. Median duration of SD was 3.9 months in each cohort. Median PFS and OS were 1.8 and 4.9 months and 1.8 and 5.9 months, respectively, for the weekly and daily schedules. Among patients receiving daily everolimus, those with a KRAS mutation experienced significantly shorter median OS (P = 0.008) and lower DCR (P = 0.035) compared with those with wild-type KRAS in exploratory biomarker analyses.

conclusionsEverolimus 70 mg/wk or 10 mg/d was well tolerated but did not confer meaningful efficacy in heavily pretreated patients with metastatic colorectal cancers. Future studies may consider evaluating everolimus in combination with other agents or in patients with dysregulation of the PI3K/Akt/mTOR pathway.

Indexed as

AdenocarcinomaAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCamptothecinClass I Phosphatidylinositol 3-KinasesColorectal NeoplasmsDisease-Free SurvivalDNA Mutational AnalysisDrug Resistance, NeoplasmEverolimusFemale5-fluoropyrimidineAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBevacizumabBRAF protein, humanCamptothecinClass I Phosphatidylinositol 3-KinasesEverolimusIrinotecanOrganoplatinum CompoundsOxaliplatinPhosphatidylinositol 3-KinasesPIK3CA protein, humanProto-Oncogene Proteins B-rafPyrimidinesSirolimus

Identifiers

PMID23743569
PMCPMC3725595
OpenAlexW2129577018

What OpenQuestion holds

Textmetadata
LicenceTDM
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.