Evidence map›Paper›PMID 25488966›Full record

Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2015

Multicenter Phase II Trial of Temsirolimus and Bevacizumab in Pancreatic Neuroendocrine Tumors.

Timothy J Hobday, Rui Qin, Diane Reidy-Lagunes, Malcolm J Moore, Jonathan Strosberg, Andreas Kaubisch, Manisha Shah, Hedy Lee Kindler, Heinz-Josef Lenz, Helen Chen and 1 more

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

Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 1 pooled it
10.7field-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

67 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.

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  13. Medication-Induced Hyperglycemia and Diabetes Mellitus: A Review of Current Literature and Practical Management Strategies.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2024
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7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Timothy J HobdayTimothy J. Hobday, Rui Qin, and Charles Erlichman, Mayo Clinic, Rochester, MN; Diane Reidy-Lagunes, Memorial Sloan Kettering Cancer Center, New York; Andreas Kaubisch, Montefiore Medical Center, Bronx, NY; Malcolm J. Moore, Princess Margaret Hospital, Toronto, Ontario, Canada; Jonathan Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Manisha Shah, Ohio State University, Columbus, OH; Hedy Lee Kindler, University of Chicago, Chicago, IL; Heinz-Josef Lenz, University of Southern California, Los Angeles, CA; and Helen Chen, National Cancer Institute, Rockville, MD. hobday.timothy@mayo.edu.
Rui QinTimothy J. Hobday, Rui Qin, and Charles Erlichman, Mayo Clinic, Rochester, MN; Diane Reidy-Lagunes, Memorial Sloan Kettering Cancer Center, New York; Andreas Kaubisch, Montefiore Medical Center, Bronx, NY; Malcolm J. Moore, Princess Margaret Hospital, Toronto, Ontario, Canada; Jonathan Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Manisha Shah, Ohio State University, Columbus, OH; Hedy Lee Kindler, University of Chicago, Chicago, IL; Heinz-Josef Lenz, University of Southern California, Los Angeles, CA; and Helen Chen, National Cancer Institute, Rockville, MD.
Diane Reidy-LagunesTimothy J. Hobday, Rui Qin, and Charles Erlichman, Mayo Clinic, Rochester, MN; Diane Reidy-Lagunes, Memorial Sloan Kettering Cancer Center, New York; Andreas Kaubisch, Montefiore Medical Center, Bronx, NY; Malcolm J. Moore, Princess Margaret Hospital, Toronto, Ontario, Canada; Jonathan Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Manisha Shah, Ohio State University, Columbus, OH; Hedy Lee Kindler, University of Chicago, Chicago, IL; Heinz-Josef Lenz, University of Southern California, Los Angeles, CA; and Helen Chen, National Cancer Institute, Rockville, MD.
Malcolm J MooreTimothy J. Hobday, Rui Qin, and Charles Erlichman, Mayo Clinic, Rochester, MN; Diane Reidy-Lagunes, Memorial Sloan Kettering Cancer Center, New York; Andreas Kaubisch, Montefiore Medical Center, Bronx, NY; Malcolm J. Moore, Princess Margaret Hospital, Toronto, Ontario, Canada; Jonathan Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Manisha Shah, Ohio State University, Columbus, OH; Hedy Lee Kindler, University of Chicago, Chicago, IL; Heinz-Josef Lenz, University of Southern California, Los Angeles, CA; and Helen Chen, National Cancer Institute, Rockville, MD.
Jonathan StrosbergTimothy J. Hobday, Rui Qin, and Charles Erlichman, Mayo Clinic, Rochester, MN; Diane Reidy-Lagunes, Memorial Sloan Kettering Cancer Center, New York; Andreas Kaubisch, Montefiore Medical Center, Bronx, NY; Malcolm J. Moore, Princess Margaret Hospital, Toronto, Ontario, Canada; Jonathan Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Manisha Shah, Ohio State University, Columbus, OH; Hedy Lee Kindler, University of Chicago, Chicago, IL; Heinz-Josef Lenz, University of Southern California, Los Angeles, CA; and Helen Chen, National Cancer Institute, Rockville, MD.
Andreas KaubischTimothy J. Hobday, Rui Qin, and Charles Erlichman, Mayo Clinic, Rochester, MN; Diane Reidy-Lagunes, Memorial Sloan Kettering Cancer Center, New York; Andreas Kaubisch, Montefiore Medical Center, Bronx, NY; Malcolm J. Moore, Princess Margaret Hospital, Toronto, Ontario, Canada; Jonathan Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Manisha Shah, Ohio State University, Columbus, OH; Hedy Lee Kindler, University of Chicago, Chicago, IL; Heinz-Josef Lenz, University of Southern California, Los Angeles, CA; and Helen Chen, National Cancer Institute, Rockville, MD.
Manisha ShahTimothy J. Hobday, Rui Qin, and Charles Erlichman, Mayo Clinic, Rochester, MN; Diane Reidy-Lagunes, Memorial Sloan Kettering Cancer Center, New York; Andreas Kaubisch, Montefiore Medical Center, Bronx, NY; Malcolm J. Moore, Princess Margaret Hospital, Toronto, Ontario, Canada; Jonathan Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Manisha Shah, Ohio State University, Columbus, OH; Hedy Lee Kindler, University of Chicago, Chicago, IL; Heinz-Josef Lenz, University of Southern California, Los Angeles, CA; and Helen Chen, National Cancer Institute, Rockville, MD.
Hedy Lee KindlerTimothy J. Hobday, Rui Qin, and Charles Erlichman, Mayo Clinic, Rochester, MN; Diane Reidy-Lagunes, Memorial Sloan Kettering Cancer Center, New York; Andreas Kaubisch, Montefiore Medical Center, Bronx, NY; Malcolm J. Moore, Princess Margaret Hospital, Toronto, Ontario, Canada; Jonathan Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Manisha Shah, Ohio State University, Columbus, OH; Hedy Lee Kindler, University of Chicago, Chicago, IL; Heinz-Josef Lenz, University of Southern California, Los Angeles, CA; and Helen Chen, National Cancer Institute, Rockville, MD.
Heinz-Josef LenzTimothy J. Hobday, Rui Qin, and Charles Erlichman, Mayo Clinic, Rochester, MN; Diane Reidy-Lagunes, Memorial Sloan Kettering Cancer Center, New York; Andreas Kaubisch, Montefiore Medical Center, Bronx, NY; Malcolm J. Moore, Princess Margaret Hospital, Toronto, Ontario, Canada; Jonathan Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Manisha Shah, Ohio State University, Columbus, OH; Hedy Lee Kindler, University of Chicago, Chicago, IL; Heinz-Josef Lenz, University of Southern California, Los Angeles, CA; and Helen Chen, National Cancer Institute, Rockville, MD.
Helen ChenTimothy J. Hobday, Rui Qin, and Charles Erlichman, Mayo Clinic, Rochester, MN; Diane Reidy-Lagunes, Memorial Sloan Kettering Cancer Center, New York; Andreas Kaubisch, Montefiore Medical Center, Bronx, NY; Malcolm J. Moore, Princess Margaret Hospital, Toronto, Ontario, Canada; Jonathan Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Manisha Shah, Ohio State University, Columbus, OH; Hedy Lee Kindler, University of Chicago, Chicago, IL; Heinz-Josef Lenz, University of Southern California, Los Angeles, CA; and Helen Chen, National Cancer Institute, Rockville, MD.
Charles ErlichmanTimothy J. Hobday, Rui Qin, and Charles Erlichman, Mayo Clinic, Rochester, MN; Diane Reidy-Lagunes, Memorial Sloan Kettering Cancer Center, New York; Andreas Kaubisch, Montefiore Medical Center, Bronx, NY; Malcolm J. Moore, Princess Margaret Hospital, Toronto, Ontario, Canada; Jonathan Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Manisha Shah, Ohio State University, Columbus, OH; Hedy Lee Kindler, University of Chicago, Chicago, IL; Heinz-Josef Lenz, University of Southern California, Los Angeles, CA; and Helen Chen, National Cancer Institute, Rockville, MD.
Memorial Sloan Kettering Cancer Center · US

Funding

Re-Engineering Translational Research at the University of ChicagoUL1TR000430 · NCATS · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2012 to 2016
$20.2M
UM1 Supplement for Early Therapeutic Trials with Phase 2 IntentUM1CA186712 · NCI · OHIO STATE UNIVERSITY · PI SUSANNE M ARNOLD, WILLIAM E. CARSON · 2014 to 2026
$19.3M
Phase 2 Clinical Trials Program for Experimental Therapeutics Clinical Trials NetworkUM1CA186686 · NCI · MAYO CLINIC ROCHESTER · PI ADJEI, ALEX A. · 2014 to 2019
$5.3M
NCATS NIH HHS UL1 TR000430NCI NIH HHS HHSN261201100070CNCI NIH HHS N01-CM-00080NCI NIH HHS UM1 CA186686NCI NIH HHS UM1 CA186712PHS HHS N01 62201PHS HHS N01 62203PHS HHS N01 62204PHS HHS N01 62205PHS HHS N01 62206PHS HHS N01 62207PHS HHS N01 62208PHS HHS N01 62209
6 · The paper itself

Abstract

purposeThere are few effective therapies for pancreatic neuroendocrine tumors (PNETs). Recent placebo-controlled phase III trials of the mammalian target of rapamycin (mTOR) inhibitor everolimus and the vascular endothelial growth factor (VEGF)/platelet-derived growth factor receptor inhibitor sunitinib have noted improved progression-free survival (PFS). Preclinical studies have suggested enhanced antitumor effects with combined mTOR and VEGF pathway-targeted therapy. We conducted a clinical trial to evaluate combination therapy against these targets in PNETs. PATIENTS AND

methodsWe conducted a two-stage single-arm phase II trial of the mTOR inhibitor temsirolimus 25 mg intravenously (IV) once per week and the VEGF-A monoclonal antibody bevacizumab 10 mg/kg IV once every 2 weeks in patients with well or moderately differentiated PNETs and progressive disease by RECIST within 7 months of study entry. Coprimary end points were tumor response rate and 6-month PFS.

resultsA total of 58 patients were enrolled, and 56 patients were eligible for response assessment. Confirmed response rate (RR) was 41% (23 of 56 patients). PFS at 6 months was 79% (44 of 56). Median PFS was 13.2 months (95% CI, 11.2 to 16.6). Median overall survival was 34 months (95% CI, 27.1 to not reached). For evaluable patients, the most common grade 3 to 4 adverse events attributed to therapy were hypertension (21%), fatigue (16%), lymphopenia (14%), and hyperglycemia (14%).

conclusionThe combination of temsirolimus and bevacizumab had substantial activity and reasonable tolerability in a multicenter phase II trial, with RR of 41%, well in excess of single targeted agents in patients with progressive PNETs. Six-month PFS was a notable 79% in a population of patients with disease progression by RECIST criteria within 7 months of study entry. On the basis of this trial, continued evaluation of combination mTOR and VEGF pathway inhibitors is warranted.

Indexed as

AdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabDisease-Free SurvivalFemaleHumansKaplan-Meier EstimateMaleMiddle AgedNeuroendocrine TumorsPancreatic NeoplasmsProtein Kinase InhibitorsSirolimusAntibodies, Monoclonal, HumanizedBevacizumabMTOR protein, humanProtein Kinase InhibitorsSirolimustemsirolimusTOR Serine-Threonine KinasesVascular Endothelial Growth Factor A

Identifiers

PMID25488966
PMCPMC4417726
OpenAlexW2168123315

What OpenQuestion holds

Textmetadata
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.