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Activating mTOR mutations in a patient with an extraordinary response on a phase I trial of everolimus and pazopanib

Wagle N, Rosenberg JE et al. · 2014 · Cancer discovery · Atlas ID WAG2014

What this study shows

An activating MTOR mutation is implicated in an extraordinary clinical response to rapalog therapy. Single-patient observation: hypothesis-generating, not evidence of a general response predictor.

Abstract

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Understanding the genetic mechanisms of sensitivity to targeted anticancer therapies may improve patient selection, response to therapy, and rational treatment designs. One approach to increase this understanding involves detailed studies of exceptional responders: rare patients with unexpected exquisite sensitivity or durable responses to therapy. We identified an exceptional responder in a phase I study of pazopanib and everolimus in advanced solid tumors.

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At a glance

Evidence type H Human study Marked H because it is direct evidence from a human clinical trial or human cohort; the code names the kind of study, not its quality -- a small, well-run trial is still H.
Study type3 - Human Observational
Model systemHuman (patient)
JournalCancer discovery
Year2014
Peer reviewedYes
Record last updated2026-07-29
SourceDOI 10.1158/2159-8290.CD-13-0353 · PMID 24625776 · Free full text (PMC4122326)

Extracted findings

InterventionEverolimus + pazopanib (mTOR inhibition)
TargetmTOR (activating mutations)
ModelHuman (patient, phase I)
EffectActivating mTOR mutations underlie an extraordinary response to everolimus in a phase I patient
DosePazopanib 400 mg daily + everolimus 5 mg daily (MTD; 600 mg + 5 mg gave dose-limiting toxicities); phase I.
Sample size9 patients enrolled (5 urothelial, others lung/carcinoid); an exceptional responder analyzed by sequencing.
Effect sizeActivating mTOR mutations underlie the extraordinary response to everolimus+pazopanib. 5/9 patients had grade >=3 toxicity (56%, 95% CI 21.2-86.3%); everolimus AUC 41% higher when combined with pazopanib.
LimitationsInference from a single exceptional responder; basis of mTOR-inhibitor sensitivity incompletely understood; short drug exposure in some.

In the Atlas

Related topics

mTOR

Cite this paper

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Wagle, N., et al. (2014). Activating mTOR mutations in a patient with an extraordinary response on a phase I trial of everolimus and pazopanib. Cancer discovery. https://doi.org/10.1158/2159-8290.CD-13-0353

@article{WAG2014,
  author       = {Wagle, N. and Rosenberg, J. E. and others},
  title        = {{Activating mTOR mutations in a patient with an extraordinary response on a phase I trial of everolimus and pazopanib}},
  journal      = {Cancer discovery},
  year         = {2014},
  doi          = {10.1158/2159-8290.CD-13-0353},
  note         = {PMID: 24625776},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper. 

Barton, O. (2026). Oliver's mTOR Atlas (record WAG2014) [Data set]. https://mtor-atlas.org/study/WAG2014/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_WAG2014,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record WAG2014},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/WAG2014/},
  doi          = {10.5281/zenodo.22059963}
}