Angiomyolipoma rebound tumor growth after discontinuation of everolimus in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis

John Bissler, Norio Nonomura, Klemens Budde, Bernard A. Zonnenberg, Michael Fischereder, Maurizio Voi, Anne Laure Louveau, Fabian Herbst, E. Martina Bebin, Paolo Curatolo, Andrea Zonta, Elena Belousova

Research output: Contribution to journalArticle

Abstract

Introduction The EXIST-2 (NCT00790400) study demonstrated the superiority of everolimus over placebo for the treatment of renal angiomyolipomas associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (LAM). This post hoc analysis of EXIST-2 study aimed to assess angiomyolipoma tumor behavior among patients who submitted to continued radiographic examination following discontinuation of everolimus in the noninterventional follow-up phase. Methods For patients who discontinued everolimus at the completion of extension phase for reasons other than angiomyolipoma progression, a single CT/MRI scan of the kidney was collected after 1 year of treatment discontinuation. Changes from baseline and from the time of everolimus discontinuation in the sum of volumes of target angiomyolipoma lesions were assessed in the non-interventional follow-up phase (data cutoff date, November 6, 2015). Results Of the 112 patients who received 1 dose of everolimus and discontinued treatment by the end of extension phase, 34 (30.4%) were eligible for participation in the non-interventional follow-up phase. Sixteen of 34 patients were evaluable for angiomyolipoma tumor behavior as they had at least one valid efficacy assessment (i.e. kidney CT/MRI scan) after everolimus discontinuation. During the non-interventional follow-up phase, compared with baseline, two patients (12.5%) experienced angiomyolipoma progression (angiomyolipoma-related bleeding [n = 1], increased kidney volume [n = 1]). Five patients out of 16 (31.3%) experienced angiomyolipoma progression when compared with the angiomyolipoma tumor assessment at everolimus discontinuation. The median (range) percentage change in angiomyolipoma tumor volume (cm3) from baseline was −70.56 (−88.30; −49.64) at time of everolimus discontinuation (n = 11), and −50.55 (−79.40; −23.16) at week 48 (n = 7) after discontinuation of everolimus. One patient death was reported due to angiomyolipoma hemorrhage. Conclusions Angiomyolipoma lesions displayed an increase in volume following discontinuation of everolimus in patients with renal angiomyolipoma or sporadic LAM associated with TSC, but there was no evidence of rapid regrowth.

Original languageEnglish (US)
Article numbere0201005
JournalPloS one
Volume13
Issue number9
DOIs
StatePublished - Sep 1 2018

Fingerprint

Lymphangioleiomyomatosis
Angiomyolipoma
Tuberous Sclerosis
sclerosis
Tumors
neoplasms
Growth
kidneys
Neoplasms
Kidney
computed tomography
lesions (animal)
hemorrhage
Everolimus
regrowth
placebos
Magnetic Resonance Imaging
Hemorrhage
death
Tumor Burden

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Angiomyolipoma rebound tumor growth after discontinuation of everolimus in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. / Bissler, John; Nonomura, Norio; Budde, Klemens; Zonnenberg, Bernard A.; Fischereder, Michael; Voi, Maurizio; Louveau, Anne Laure; Herbst, Fabian; Bebin, E. Martina; Curatolo, Paolo; Zonta, Andrea; Belousova, Elena.

In: PloS one, Vol. 13, No. 9, e0201005, 01.09.2018.

Research output: Contribution to journalArticle

Bissler, J, Nonomura, N, Budde, K, Zonnenberg, BA, Fischereder, M, Voi, M, Louveau, AL, Herbst, F, Bebin, EM, Curatolo, P, Zonta, A & Belousova, E 2018, 'Angiomyolipoma rebound tumor growth after discontinuation of everolimus in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis', PloS one, vol. 13, no. 9, e0201005. https://doi.org/10.1371/journal.pone.0201005
Bissler, John ; Nonomura, Norio ; Budde, Klemens ; Zonnenberg, Bernard A. ; Fischereder, Michael ; Voi, Maurizio ; Louveau, Anne Laure ; Herbst, Fabian ; Bebin, E. Martina ; Curatolo, Paolo ; Zonta, Andrea ; Belousova, Elena. / Angiomyolipoma rebound tumor growth after discontinuation of everolimus in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. In: PloS one. 2018 ; Vol. 13, No. 9.
@article{5cdaf8269d6f4c5192f312d33b06e8f3,
title = "Angiomyolipoma rebound tumor growth after discontinuation of everolimus in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis",
abstract = "Introduction The EXIST-2 (NCT00790400) study demonstrated the superiority of everolimus over placebo for the treatment of renal angiomyolipomas associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (LAM). This post hoc analysis of EXIST-2 study aimed to assess angiomyolipoma tumor behavior among patients who submitted to continued radiographic examination following discontinuation of everolimus in the noninterventional follow-up phase. Methods For patients who discontinued everolimus at the completion of extension phase for reasons other than angiomyolipoma progression, a single CT/MRI scan of the kidney was collected after 1 year of treatment discontinuation. Changes from baseline and from the time of everolimus discontinuation in the sum of volumes of target angiomyolipoma lesions were assessed in the non-interventional follow-up phase (data cutoff date, November 6, 2015). Results Of the 112 patients who received 1 dose of everolimus and discontinued treatment by the end of extension phase, 34 (30.4{\%}) were eligible for participation in the non-interventional follow-up phase. Sixteen of 34 patients were evaluable for angiomyolipoma tumor behavior as they had at least one valid efficacy assessment (i.e. kidney CT/MRI scan) after everolimus discontinuation. During the non-interventional follow-up phase, compared with baseline, two patients (12.5{\%}) experienced angiomyolipoma progression (angiomyolipoma-related bleeding [n = 1], increased kidney volume [n = 1]). Five patients out of 16 (31.3{\%}) experienced angiomyolipoma progression when compared with the angiomyolipoma tumor assessment at everolimus discontinuation. The median (range) percentage change in angiomyolipoma tumor volume (cm3) from baseline was −70.56 (−88.30; −49.64) at time of everolimus discontinuation (n = 11), and −50.55 (−79.40; −23.16) at week 48 (n = 7) after discontinuation of everolimus. One patient death was reported due to angiomyolipoma hemorrhage. Conclusions Angiomyolipoma lesions displayed an increase in volume following discontinuation of everolimus in patients with renal angiomyolipoma or sporadic LAM associated with TSC, but there was no evidence of rapid regrowth.",
author = "John Bissler and Norio Nonomura and Klemens Budde and Zonnenberg, {Bernard A.} and Michael Fischereder and Maurizio Voi and Louveau, {Anne Laure} and Fabian Herbst and Bebin, {E. Martina} and Paolo Curatolo and Andrea Zonta and Elena Belousova",
year = "2018",
month = "9",
day = "1",
doi = "10.1371/journal.pone.0201005",
language = "English (US)",
volume = "13",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - Angiomyolipoma rebound tumor growth after discontinuation of everolimus in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis

AU - Bissler, John

AU - Nonomura, Norio

AU - Budde, Klemens

AU - Zonnenberg, Bernard A.

AU - Fischereder, Michael

AU - Voi, Maurizio

AU - Louveau, Anne Laure

AU - Herbst, Fabian

AU - Bebin, E. Martina

AU - Curatolo, Paolo

AU - Zonta, Andrea

AU - Belousova, Elena

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Introduction The EXIST-2 (NCT00790400) study demonstrated the superiority of everolimus over placebo for the treatment of renal angiomyolipomas associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (LAM). This post hoc analysis of EXIST-2 study aimed to assess angiomyolipoma tumor behavior among patients who submitted to continued radiographic examination following discontinuation of everolimus in the noninterventional follow-up phase. Methods For patients who discontinued everolimus at the completion of extension phase for reasons other than angiomyolipoma progression, a single CT/MRI scan of the kidney was collected after 1 year of treatment discontinuation. Changes from baseline and from the time of everolimus discontinuation in the sum of volumes of target angiomyolipoma lesions were assessed in the non-interventional follow-up phase (data cutoff date, November 6, 2015). Results Of the 112 patients who received 1 dose of everolimus and discontinued treatment by the end of extension phase, 34 (30.4%) were eligible for participation in the non-interventional follow-up phase. Sixteen of 34 patients were evaluable for angiomyolipoma tumor behavior as they had at least one valid efficacy assessment (i.e. kidney CT/MRI scan) after everolimus discontinuation. During the non-interventional follow-up phase, compared with baseline, two patients (12.5%) experienced angiomyolipoma progression (angiomyolipoma-related bleeding [n = 1], increased kidney volume [n = 1]). Five patients out of 16 (31.3%) experienced angiomyolipoma progression when compared with the angiomyolipoma tumor assessment at everolimus discontinuation. The median (range) percentage change in angiomyolipoma tumor volume (cm3) from baseline was −70.56 (−88.30; −49.64) at time of everolimus discontinuation (n = 11), and −50.55 (−79.40; −23.16) at week 48 (n = 7) after discontinuation of everolimus. One patient death was reported due to angiomyolipoma hemorrhage. Conclusions Angiomyolipoma lesions displayed an increase in volume following discontinuation of everolimus in patients with renal angiomyolipoma or sporadic LAM associated with TSC, but there was no evidence of rapid regrowth.

AB - Introduction The EXIST-2 (NCT00790400) study demonstrated the superiority of everolimus over placebo for the treatment of renal angiomyolipomas associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (LAM). This post hoc analysis of EXIST-2 study aimed to assess angiomyolipoma tumor behavior among patients who submitted to continued radiographic examination following discontinuation of everolimus in the noninterventional follow-up phase. Methods For patients who discontinued everolimus at the completion of extension phase for reasons other than angiomyolipoma progression, a single CT/MRI scan of the kidney was collected after 1 year of treatment discontinuation. Changes from baseline and from the time of everolimus discontinuation in the sum of volumes of target angiomyolipoma lesions were assessed in the non-interventional follow-up phase (data cutoff date, November 6, 2015). Results Of the 112 patients who received 1 dose of everolimus and discontinued treatment by the end of extension phase, 34 (30.4%) were eligible for participation in the non-interventional follow-up phase. Sixteen of 34 patients were evaluable for angiomyolipoma tumor behavior as they had at least one valid efficacy assessment (i.e. kidney CT/MRI scan) after everolimus discontinuation. During the non-interventional follow-up phase, compared with baseline, two patients (12.5%) experienced angiomyolipoma progression (angiomyolipoma-related bleeding [n = 1], increased kidney volume [n = 1]). Five patients out of 16 (31.3%) experienced angiomyolipoma progression when compared with the angiomyolipoma tumor assessment at everolimus discontinuation. The median (range) percentage change in angiomyolipoma tumor volume (cm3) from baseline was −70.56 (−88.30; −49.64) at time of everolimus discontinuation (n = 11), and −50.55 (−79.40; −23.16) at week 48 (n = 7) after discontinuation of everolimus. One patient death was reported due to angiomyolipoma hemorrhage. Conclusions Angiomyolipoma lesions displayed an increase in volume following discontinuation of everolimus in patients with renal angiomyolipoma or sporadic LAM associated with TSC, but there was no evidence of rapid regrowth.

UR - http://www.scopus.com/inward/record.url?scp=85053158980&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053158980&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0201005

DO - 10.1371/journal.pone.0201005

M3 - Article

VL - 13

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e0201005

ER -