Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial

Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, Belousova E, Sauter M, Nonomura N, Brakemeier S, de Vries PJ, Whittemore VH, …, Budde K · 2013 · Lancet · Atlas ID BIS2013

What this study shows

The companion phase 3 RCT (n=118) to EXIST-1, targeting kidney tumors (angiomyolipomas) in tuberous sclerosis and LAM. Everolimus shrank them by >=50% in 42% of patients versus 0% on placebo. Together EXIST-1 and -2 sealed everolimus as a disease-modifying therapy across multiple TSC tumor types.

Cited on mTOR drugs in development: AV078

Abstract

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Angiomyolipomas are slow-growing tumours associated with constitutive activation of mammalian target of rapamycin (mTOR), and are common in patients with tuberous sclerosis complex and sporadic lymphangioleiomyomatosis. The insidious growth of these tumours predisposes patients to serious complications including retroperitoneal haemorrhage and impaired renal function. Everolimus, a rapamycin derivative, inhibits the mTOR pathway by acting on the mTOR complex 1.

Read the full abstract on PubMed →

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 type	2 - Human Clinical Trial
Model system	Humans, phase 3 RCT (n=118, TSC/LAM)
Journal	Lancet
Year	2013
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/S0140-6736(12)61767-X · PMID 23312829

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Everolimus
Target	mTORC1
Model	Human – phase 3 RCT (EXIST-2, n=118, TSC/LAM)
Effect	Everolimus reduced angiomyolipoma size vs placebo in TSC/LAM

In the Atlas

Links in the pathway map

Supports Everolimus inhibits Renal angiomyolipoma
Supports Everolimus inhibits mTORC1
Supports Everolimus inhibits Tuberous sclerosis complex

Answers that reference this study

Discussed in the plain-language answer How does mTOR connect to cancer?.

Cite this paper

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Bissler, J. J., Kingswood, J. C., Radzikowska, E., Zonnenberg, B. A., Frost, M., Belousova, E., Sauter, M., Nonomura, N., Brakemeier, S., de Vries, P. J., Whittemore, V. H., Chen, D., Sahmoud, T., Shah, G., Lincy, J., Lebwohl, D., & Budde, K. (2013). Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. https://doi.org/10.1016/S0140-6736(12)61767-X

@article{BIS2013,
  author       = {Bissler, J. J. and Kingswood, J. C. and Radzikowska, E. and Zonnenberg, B. A. and Frost, M. and Belousova, E. and Sauter, M. and Nonomura, N. and Brakemeier, S. and de Vries, P. J. and Whittemore, V. H. and Chen, D. and Sahmoud, T. and Shah, G. and Lincy, J. and Lebwohl, D. and Budde, K.},
  title        = {{Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial}},
  journal      = {Lancet},
  year         = {2013},
  doi          = {10.1016/S0140-6736(12)61767-X},
  note         = {PMID: 23312829},
}

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 BIS2013) [Data set]. https://mtor-atlas.org/study/BIS2013/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_BIS2013,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record BIS2013},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/BIS2013/},
  doi          = {10.5281/zenodo.22059963}
}

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